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Cancer Types   /   Lymphomas   /   Non-Hodgkin's Disease   /   NCI Resources

NCI CANCERLIT® Search: Therapy of Non-Hodgkin|s Lymphoma - September 2001

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Last Modified: November 1, 2001

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CancerMail from the National Cancer Institute

1
UI - 21174310
AU - Gazitt Y; Shaughnessy P; Devore P
TI - Mobilization of dendritic cells and NK cells in non-Hodgkin's lymphoma patients mobilized with different growth factors.
SO - J Hematother Stem Cell Res 2001 Feb;10(1):177-86
AD - University of Texas, Health Science Center, San Antonio, TX 78286, USA.
Conflicting results have been reported regarding the effect of various growth factors on the mobilization of natural killer (NK) cells and dendritic cells in patients undergoing stem cell mobilization for autotransplantation. We compared the extent of mobilization of NK cells and dendritic cells in non-Hodgkin's (NHL) patients undergoing mobilization with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, or GM-CSF followed by G-CSF. Overall, 35 patients were studied. NK cells and dendritic were quantitated by flow cytometry. NK cells were defined as the sum of CD56(+) cells and CD56/CD16(+) cells. Dendritic cells were defined as the sum of CD80(+) and CD80(+)/CD14(+) cells. NK activity was determined by by microcytotoxicity assay. NK activity correlated well with the total amount of CD56(+) cells mobilized to the peripheral blood. Patients in the three arms of the study mobilized similar amounts of NK cells and NK activity, and patients who lacked NK activity in the peripheral blood, before mobilization, lacked NK activity in their apheresis collections. In contrast to NK cell mobilization, mobilization of dendritic cells/kg was three- to five-fold higher in patients mobilized with GM-CSF-containing regimens compared to patients mobilized with G-CSF alone. We conclude that GM-CSF-containing mobilization regimens are superior for dendritic cell mobilization but similar in the mobilization of NK cells. Therefore, we recommend using GM-CSF-containing regimens for patients undergoing ex vivo or in vivo manipulation of dendritic cells.

2
UI - 21319818
AU - Stein RS; Greer JP; Goodman S; Brandt SJ; Morgan DS; Macon WR; McCurley TL; Wolff SN
TI - Limited efficacy of intensified preparative regimens and autologous transplantation as salvage therapy in high grade non-Hodgkin's lymphoma.
SO - Leuk Lymphoma 2001 Feb;40(5-6):521-8
AD - Department of Medicine, Vanderbilt University School of Medicine, and VA Medical Center, Nashville, TN 37232, USA. steinrs@ctrvax.vanderbilt.edu
Between 9/86 and 6/98, 22 patients with relapsed or refractory high grade lymphoma received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used--cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (N=17) and cyclophosphamide, BCNU, etoposide (CBV) (N=5). For all patients undergoing autologous transplantation, 5 year actuarial survival (S) and 5 year event free survival (EFS) were only 18% +/- 8%. Treatment related mortality was 14% overall but only 8% in patients receiving G-CSF or GM-CSF. Survival was significantly inferior to the survival observed in a concurrent series of patients with intermediate grade lymphoma, 34% +/- 6%, p < .05. Using high dose therapy in conjunction with autologous transplantation at the time of relapse may not be as valuable a strategy in high-grade lymphoma as in intermediate grade lymphoma although most studies combine the two disorders. Alternative strategies for the use of transplantation in high grade lymphoma, such as the use of transplantation as consolidation therapy, need to be investigated.

3
UI - 21319819
AU - Cartron G; Voillat L; Desablens B; Le Maignan C; Milpied N; Foussard C; Dugay J; Maakaroun A; De Muret A; Colombat P; GOELAMS Group
TI - Continuous infusion of vincristine-doxorubicin with bolus of dexamethasone(VAD) alternated with CHEP in the treatment of patients over 60 years old with aggressive non-Hodgkin's lymphoma.
SO - Leuk Lymphoma 2001 Feb;40(5-6):529-40
AD - Department of Hematology of Tours, France. Guillaume.Cartron@med.univ-tours.fr
This prospective study was undertaken to evaluate the efficacy and toxicity of combination chemotherapy with alternating cycles of vincristine, doxorubicin and dexamethasone (VAD) and cyclophophamide, doxorubicin, etoposide and prednisone (CHEP) in patients over 60 years old with previously untreated and advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy. Eighty one consecutive, patients with NHL referred from April 1992 to October 1997 to GOELAMS centers were enrolled in this study and their outcome updated to June 1, 1999. Of 81 enrolled patients, 77 were eligible and assessable for response. The median age was 70 years (61 to 78), 85.7% were stage III or IV, 39% were of performance status > or = 2, 27.3% > or = 2 involved extra-nodal sites and 57.3% had higher LDH levels than normal. The immunophenotype was B in 87% and T in 13%. Fifty-one (66.2%) patients received the scheduled eight cycles of therapy and treatment was withdrawn in only 6 patients (7.8%) because of toxicity. Neutropenia grade 3-4 occurred in 11.1% after VAD courses vs 40.6% after CHEP courses. The mean cumulative dose of doxorubicin was 269 mg/m2 and the relative dose intensity was 84%. The overall response and complete response rates were 66.2% and 51.9% respectively, and after a median follow-up of 52 months the 3 year overall survival (OS) and event-free survival rates (EFS) were 43.5% and 33.0% respectively. In multivariate analysis, OS and EFS were statistically influenced by IPI (p = 3 x 10(-3); p < 1 x 10(-4)) and phenotype (p = 2 x 10(-3); p < 1 x 10(-4)). Our findings support the alternation of 4 courses of VAD and CHEP as it is well tolerated in patients over 60 years old with advanced intermediate- or high-grade NHL and provides response and survival rates comparable to 6 courses of CHOP.

4
UI - 21319822
AU - Wirt DP; Giles FJ; Oken MM; Solal-Celigny P; Beck JR
TI - Cost-Effectiveness of interferon alfa-2b added to chemotherapy for high-tumor-burden follicular non-Hodgkin's lymphoma.
SO - Leuk Lymphoma 2001 Feb;40(5-6):565-79
AD - Baylor College of Medicine, Houston, Texas, USA.
Recent data from GELF (Groupe d'Etude des Lymphomes Folliculaires) have shown that the addition of interferon alfa-2b (IFN) to a doxorubicin-containing regimen (CHVP: cyclophosphamide, doxorubicin, teniposide and prednisone) prolongs both progression-free survival and overall survival in high-tumor-burden follicular non-Hodgkin's lymphoma. This gain must be weighed against the incremental toxicity and cost of IFN over CHVP alone and the objective here was, to determine the marginal cost-effectiveness of additive IFN in the specific setting of high-tumor-burden follicular non-Hodgkin's lymphoma. Meta-analysis of GELF trial results employing a Markov model was used with three health states: No Progression, Progressive Disease, and Death. Treatment response, survival and toxicity data are drawn from the GELF study. The current study is based on the final analysis of 242 patients (J Clin Oncol 1998;16:2332-2338), with a six year median follow-up for overall survival (median overall survival: not reached for CHVP + IFN vs 5.6 years for CHVP Only, p = 0.008). Measurements: Quality of life data (utilities) are taken from studies with similar dosing of IFN, from Q-TwiST (quality adjusted time without symptoms or toxicity) analysis of the GELF data and from a panel of experts gathered to develop treatment models for high-tumor-burden follicular non-Hodgkin's lymphoma. Costs and quality-adjusted years of life saved were discounted at 3% per annum. Setting: Costs determined for university medical centers in the United States. Results showed that, at the median cohort age of 52, IFN add 9.9 quality-adjusted months at an added cost of $13,900 (marginal cost-effectiveness of $16,900 per quality-adjusted life year, or QALY). A more complex, two-stage model approximates the actual cohort survival curves much better than a simple, one-stage model, but both models yield essentially the same marginal cost-effectiveness. Sensitivity analysis to quality of life on IFN shows marginal cost-effectiveness ranging from $15,200/QALY (no penalty for IFN) to $21,300/QALY (20% quality adjustment, greater than that reported). The model is quite insensitive to the probability of IFN toxicity. The model is moderately sensitive to the efficacy of IFN in delaying progression, particularly in the first 18 months (pProgI), but the marginal cost-effectiveness does not rise to $50,000/QALY until pProgI increases 220% from the baseline. Although the model is moderately sensitive to the cost of IFN (cIFN), marginal cost-effectiveness is below $50,000/QALY for values of cIFN below $2580/month (baseline cIFN = $850/month, corresponding to a marginal cost-effectiveness of $16,900/QALY in the baseline case). If the model is modified to reflect the 14% overall survival advantage at five years found in trials utilizing more intensive initial chemotherapy (including the GELF trial), then the marginal cost-effectiveness drops to $11,900/QALY in the baseline case. In condusion, based on data from the GELF study, low-dose interferon alfa-2b is cost-effective when added to CHVP therapy in the treatment of high-tumor-burden follicular non-Hodgkin's lymphoma. The analysis is robust: the model employs very conservative assumptions, and additive IFN remains cost-effective over wide ranges of variables in sensitivity analyses. The marginal cost-effectiveness is best expressed as being in the range of $12,000/QALY to $17,000/QALY in the baseline case. A simple Markov model can be used to describe treatment regimens with distinct periods of therapy.

5
UI - 21376181
AU - Tsang RW; Gospodarowicz MK; Pintilie M; Bezjak A; Wells W; Hodgson DC; Crump M
TI - Stage I and II MALT lymphoma: results of treatment with radiotherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1258-64
AD - Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada. richard.tsang@rmp.uhn.on.ca
PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT). PATIENTS AND METHODS: Seventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years). RESULTS: A complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients). CONCLUSION: Localized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.

6
UI - 21379851
AU - Ottonello L; Epstein AL; Mancini M; Tortolina G; Dapino P; Dallegri F
TI - Chimaeric Lym-1 monoclonal antibody-mediated cytolysis by neutrophils from G-CSF-treated patients: stimulation by GM-CSF and role of Fc gamma -receptors.
SO - Br J Cancer 2001 Aug 3;85(3):463-9
AD - Department of Internal Medicine, University of Genova Medical School, Viale Benedetto XV n.6I-16132, Genova, Italy.
Chimaeric Lym-1 (chLym-1) is a monoclonal antibody generated by fusing the variable region genes of murine Lym-1 to human gamma1 and kappa constant regions. Owing to its selectivity and avidity for human malignant B cells, it is an attractive candidate for developing immune-interventions in B-lymphomas. In the attempt to identify rational bases for optimizing potential chLym-1 related therapeutic approaches, we studied the ability of this ch-mAb to trigger neutrophil-mediated Raji cell cytolysis in cooperation with two neutrophil-related cytokines, G-CSF and GM-CSF. ChLym-1 triggered low levels of cytolysis by normal neutrophils but induced consistent cytolysis in neutrophils from individuals treated with G-CSF. When exposed to GM-CSF, neutrophils from subjects treated with G-CSF became potent effectors, also leading to 75% lysis. By using mAbs specific for distinct FcgammaRs, normal neutrophils were inhibited by mAb IV.3, suggesting the intervention of FcgammaRII, constitutively expressed on the cells. On the other hand, neutrophils from patients treated with G-CSF were inhibited by mAb IV.3 plus mAb 197, a finding consistent with a cooperative intervention of FCgammaRII and G-CSF-induced FcgammaRI. The anti-FcgammaRIII mAb 3G8 promoted significant enhancement of the neutrophil cytolytic efficiency. Therefore, neutrophil FcgammaRIII behaves as a down-regulator of the cytolytic potential. The present findings suggest new attempts to develop mAb-based and G-CSF/GM-CSF combined immune-interventions in B lymphomas.

7
UI - 21255263
AU - Ruskone-Fourmestraux A; Rambaud JC
TI - Gastrointestinal lymphoma: prevention and treatment of early lesions.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):337-54
AD - Service de Gastroenterologie, Hotel Dieu, 1, Place Parvis Notre Dame, Paris, cedex 04, 75181, France.
Gastrointestinal lymphomas comprise a group of distinct clinicopathological entities. Differences in lifestyle and environmental factors between countries could account for the variety in the distribution of the main subtypes: low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue type, alpha-chain disease and enteropathy (coeliac disease)-associated T-cell lymphoma (EATL). The possibility of preventing these lymphomas implies a knowledge of their natural history together with an identification of potential predisposing factors. The development of the lymphoid hyperplasia and subsequently low-grade lymphoma with the possibility of high-grade transformation is a multifactorial process involving both antigenic and host-related factors. The pathogenic role of Helicobacter pylori and gluten has been demonstrated in gastric lymphoma and enteropathy-associated T-cell lymphoma respectively, while environmental factors, especially non-specific bacterial ones, may play a major role in the pathogenesis of alpha-chain disease. The most difficult task in preventing these lymphomas is the recognition of early lesions likely to regress after the removal of the exogenous stimulus. Copyright 2001 Harcourt Publishers Ltd.

8
UI - 21225872
AU - Stafford SL; Kozelsky TF; Garrity JA; Kurtin PJ; Leavitt JA; Martenson JA; Habermann TM
TI - Orbital lymphoma: radiotherapy outcome and complications.
SO - Radiother Oncol 2001 May;59(2):139-44
AD - Division of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.
BACKGROUND AND PURPOSE: Orbital non-Hodgkin's lymphomas (NHL) have traditionally been treated with radiation. Forty-eight patients presenting with orbital NHL were treated with radiation and were evaluated for local control, overall survival, cause-specific survival, and complications. MATERIALS AND METHODS: Forty-five patients had low-grade and 3 patients had intermediate-grade histologic findings. Orbit-only disease occurred in 22 patients, the conjunctiva in 16, both in five, and lacrimal gland only in five. Patient age ranged from 35 to 94 years (median, 68). Ann Arbor stages were cIEA (34), cIIEA (six), cIIIEA (two), and cIVEA (six). Radiation doses ranged between 15 and 53.8 Gy (median, 27.5 Gy). RESULTS: Follow-up ranged from 0.14 to 18.23 years (median, 5.35). Median overall survival and cause-specific survival were 6.5 and 15.5 years, respectively. Patients with clinical stage I or II disease had significantly better overall and cause-specific survival than patients with stage III or IV disease. Ten-year relapse-free survival in 41 patients with stage I or II disease was 66%. However, there was continued downward pressure on relapse-free survival out to 18 years. One local failure occurred. Twenty-five patients sustained acute complications. There were 17 minor and four major late complications. All major late complications occurred with doses more than 35 Gy. CONCLUSIONS: Excellent local control with radiation doses ranging from 15 to 30 Gy is achieved. Patients with stage I or II disease have better overall and cause-specific survival than patients with stage III or IV disease. Late relapse occurs in sites other than the treated orbit, even in patients with early-stage disease. Doses 35 Gy or higher result in significant late complications and are therefore not indicated for patients with low-grade tumors.

9
UI - 21225873
AU - Pelloski CE; Wilder RB; Ha CS; Hess MA; Cabanillas FF; Cox JD
TI - Clinical stage IEA-IIEA orbital lymphomas: outcomes in the era of modern staging and treatment.
SO - Radiother Oncol 2001 May;59(2):145-51
AD - Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
BACKGROUND AND PURPOSE: The present study examines outcomes in patients with primary orbital lymphomas who underwent complete staging. MATERIALS AND METHODS: From 1978 to 1997, 21 adult patients at the M.D. Anderson Cancer Center had stage IEA-IIEA orbital non-Hodgkin's lymphomas based on staging that included computed tomography scans. Sixteen (76%) patients had working formulation low-grade lymphomas, and five (24%) had aggressive lymphomas. Fourteen of 16 (88%) patients with low-grade lymphomas were treated with radiotherapy alone, and four of five (80%) patients with aggressive lymphomas were treated using combination chemotherapy with or without radiotherapy. Total radiotherapy doses ranged from 30.0 to 40.0 Gy using daily 1.5-2.0 Gy fractions. RESULTS: The median follow-up was 84 months. For the low-grade lymphomas, the 5-year local control, progression-free survival, and overall survival rates were 100, 100, and 92%, respectively. For the seven low-grade lymphomas treated with radiotherapy alone to 30.0 Gy in 20 fractions, the 5-year local control, progression-free, and overall survival rates were 100, 100, and 75%, respectively. The 5-year incidence of complications, which were typically mild, in eyes irradiated to 30 Gy in 20 fractions versus higher biologically effective doses were 25 and 38%, respectively (P = 0.62). Of the five patients with aggressive lymphomas, none of the four who underwent chemotherapy with or without radiotherapy relapsed (all four remain alive), whereas the one treated with radiotherapy alone for stage IEA disease experienced a distant relapse. CONCLUSIONS: In patients with low-grade lymphomas, a good therapeutic ratio was obtained with low-dose radiotherapy alone. In patients with aggressive lymphomas, chemotherapy with or without radiotherapy resulted in excellent local control, progression-free survival, and overall survival; however, the statistical power was limited.

10
UI - 21265652
AU - Hsiao HH; Liu TC; Chang CS; Sue YC; Chen TP; Lin SF
TI - Secondary chronic myelogenous leukemia after autologous peripheral blood stem cell transplantation for lymphoma.
SO - Int J Hematol 2001 Jan;73(1):126-8
AD - Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan.
A 31-year-old woman was diagnosed with intestinal lymphoma (high-grade mucosa-associated lymphoid tissue lymphoma, stage IIE) in September 1996. Eleven courses of chemotherapy were administered, but the results were poor. She received autologous peripheral blood stem cell transplantation (PBSCT) in September 1997. Leukocytosis was noted, and chronic myelogenous leukemia was diagnosed 8 months after the PBSCT, progressing to blast phase 10 months later. We report this case because secondary chronic myelogenous leukemia after stem cell transplantation is rare.

11
UI - 21265624
AU - Igarashi T; Ohtsu T; Fujii H; Sasaki Y; Morishima Y; Ogura M; Kagami Y; Kinoshita T; Kasai M; Kiyama Y; Kobayashi Y; Tobinai K; IDEC-C2B8 Study Group
TI - Re-treatment of relapsed indolent B-cell lymphoma with rituximab.
SO - Int J Hematol 2001 Feb;73(2):213-21
AD - Hematology and Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.

12
UI - 21265632
AU - Fukuno K; Tsurumi H; Yamada T; Oyama M; Moriwaki H
TI - Graft failure due to hemophagocytic syndrome after autologous peripheral blood stem cell transplantation.
SO - Int J Hematol 2001 Feb;73(2):262-5
AD - Department of Internal Medicine, Kisogawa Hospital, Aichi, Japan.
Hemophagocytic syndrome (HPS) after hematopoietic stem cell transplantation can occasionally cause graft failure. We describe a female patient with B-cell non-Hodgkin's lymphoma (NHL) with graft failure due to HPS 12 days after autologous peripheral blood stem cell transplantation (PBSCT). Autologous PBSCT was carried out during unconfirmed/uncertain complete remission according to the Cotswolds classification after 6 cycles of biweekly (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and 3 courses of salvage chemotherapy including etoposide. The patient developed a high fever on day 2 post-PBSCT. Her white blood cell count rose to 0.9 x 10(9)/L on day 10 post-PBSCT, but then began to decrease. A bone marrow aspirate on day 12 post-PBSCT revealed an increase in the number of benign histiocytes with hemophagocytosis, and the patient was diagnosed with HPS. Although high-dose methylprednisolone therapy was continued, her white blood cell count further decreased to 0.3 x 10(9)/L, and the patient died of multiple organ failure on day 29 post-PBSCT. A computed tomography scan did not identify recurrent NHL, and necropsy specimens from the bone marrow, liver, and kidney revealed no neoplastic infiltration. Bone marrow necropsy showed marked hypocellularity with active histiocytic hemophagocytosis. HPS may have been induced by infection with methicillin-resistant Staphylococcus aureus rather than by lymphoma-associated HPS.

13
UI - 21353431
AU - Kitamura K
TI - [Therapeutic policy for malignant lymphoma of the aged]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):1010-8

14
UI - 21353445
AU - Tobinai K
TI - [Treatment of B cell lymphoma by using monoclonal antibodies]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):1106-11

15
UI - 21353429
AU - Hotta T
TI - [Standard treatment of malignant lymphoma (Hodgkin's and non-Hodgkin's lymphoma)]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):997-1002

16
UI - 21361153
AU - Porrata LF; Gertz MA; Inwards DJ; Litzow MR; Lacy MQ; Tefferi A; Gastineau DA; Dispenzieri A; Ansell SM; Micallef IN; Geyer SM; Markovic SN
TI - Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma.
SO - Blood 2001 Aug 1;98(3):579-85
AD - Division of Hematology, Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)

17
UI - 21397514
AU - Tvrdek M; Kletensky J; Svoboda S
TI - Aplasia of the breast--reconstruction using a free tram flap.
SO - Acta Chir Plast 2001;43(2):39-41
AD - Department of Plastic Surgery, University Hospital Kralovske Vinohrady, Third Medical Faculty, Charles University, Prague, Czech Republic.
Breast aplasia and hypoplasia are found most frequently in Poland's syndrome but may also be the consequence of damage to the germ of the mammary gland in childhood. The authors present two cases of breast aplasia in which reconstruction was implemented by free transfer of a TRAM flap. The internal mammary vessels were used as recipient vessels, the condition of which was tested before surgery by Doppler. In both instances the reconstruction was implemented at the age of 19 years, and subsequently the areolomammillary complex was created and the contralateral breast corrected to achieve symmetry. The use of autologous tissue in the form of a free TRAM flap provides, in this indication, very good results that are permanent, and the problems associated with the use of implants are eliminated.

18
UI - 21411406
AU - Vittorio CC; Rook AH; French LE; Shapiro M; Lehrer MS; Junkins-Hopkins JM
TI - Therapeutic advances in biological response modifiers in the treatment of cutaneous T-cell lymphoma.
SO - BioDrugs 2001;15(7):431-7
AD - Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Cutaneous T-cell lymphoma (CTCL) is most often a skin-infiltrating malignancy of clonal CD4+ T-cells. Therapy is based on staging and the likelihood of progression. Biological response modifiers and chemotherapeutic agents are used to preserve the integrity of the host antitumour response while selectively targeting the malignant cells. The biological response-modifying treatment options currently used to treat CTCL are bexarotene, denileukin diftitox, interferon-alpha, interferon-gamma and interleukin-12, as well as extracorporeal photopheresis and phototherapy. A combination therapy approach maximises response in patients with advanced CTCL. Biological response modifiers in combination with photopheresis are used for patients with the leukaemic phase of the disease. Among the majority of patients with advanced stage disease so treated, immune response augmentation appears to prolong survival. Future areas of research should assess not only survival and optimal treatment combinations, but also quality of life during the treatment period.

19
UI - 21420145
AU - Seyfarth B; Kuse R; Sonnen R; Glass B; Schmitz N; Dreger P
TI - Autologous stem cell transplantation for follicular lymphoma: no benefit for early transplant?
SO - Ann Hematol 2001 Jul;80(7):398-405
AD - Second Department of Medicine, University of Kiel, Germany.
Autologous stem cell transplantation (SCT) is widely used as salvage treatment for patients with relapsed follicular lymphoma (FL). Although SCT can induce prolonged remissions, it does not appear to be curative in the vast majority of patients. The purpose of this study was to investigate if incorporation of SCT into first-line therapy can improve its efficacy. Fifty-five patients underwent sequential high-dose therapy as up-front (n=33) or salvage treatment (n=22) for advanced stage FL at our institution. Treatment consisted of intensive chemotherapy with dexamethasone, carmustine (BCNU), etoposide, cytarabine, and melphalan (Dexa-BEAM) for mobilization of peripheral stem cells and reduction of tumor load, followed by one of three different myeloablative regimens and SCT. With a median follow-up of 4 years, projected event-free survival (EFS) and overall survival (OS) at 4 years post transplant was 59% and 84%, respectively, with no evidence of plateau in the survival curves. By univariate and multivariate analysis weighing age, sex, stage, BM and extranodal involvement, timing of transplant, ex vivo purging, and conditioning regimen [total body irradiation (TBI) vs non-TBI], the only significant factor predicting for superior EFS and OS was up-front vs salvage transplant (4-year EFS 76% vs 38%, p=0.02; 4-year OS 92% vs 73%, p=0.033). However, when calculated from diagnosis, EFS and OS of the up-front and salvage groups were virtually identical, implying that the longer survival post SCT in the up-front group was completely compensated by the longer interval between diagnosis and transplant in the salvage group. Median OS from diagnosis was 13.5 years. Except for one case of anaplastic large cell lymphoma, secondary neoplasms have not occurred to date. In conclusion, our data indicate that SCT might improve the prognosis of patients with disseminated FL, although it is probably not curative even if applied early during the course of the disease. The optimum timing of SCT remains to be determined by the ongoing randomized multicenter trial of the German Low-grade Lymphoma Study Group. The impact of radiotherapy on the success of SCT does not seem to be as essential as originally believed.

20
UI - 21420146
AU - Peters FP; Fickers MM; Erdkamp FL; Wals J; Wils JA; Schouten HC
TI - The effect of optimal treatment on elderly patients with aggressive non-Hodgkin's lymphoma: more patients treated with unaffected response rates.
SO - Ann Hematol 2001 Jul;80(7):406-10
AD - Maasland Hospital Sittard, University Hospital Maastricht, Department of Internal Medicine, The Netherlands. f.erdkamp@orbisconcern.nl
A substantial part of elderly patients (with good performance) with intermediate or high-grade non-Hodgkin's lymphoma (NHL) are not treated with the standard chemotherapy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). If NHL patients are not treated with CHOP, the outcome is inferior. By adding granulocyte colony-stimulating factor (G-CSF) to CHOP chemotherapy, we aimed at treating more patients with less toxicity. We performed a multicenter population-based study (in the southeast of the Netherlands) in which elderly patients (> or = 60 years) with intermediate or high-grade stage > or = IIB NHL were treated with CHOP chemotherapy and growth factor G-CSF to increase the number of patients treated according to standard protocols. We also evaluated elderly NHL patients who were not treated with CHOP chemotherapy. Adequate therapy was defined as > or = six cycles or a total of five cycles when complete remission was achieved after three cycles. Seventy-nine NHL patients fulfilled the selection criteria. The patients were treated with CHOP plus G-CSF (n=46), CHOP (n=19), cyclophosphamide, vincristine, and prednisone (COP) (n=2), chlorambucil and prednisone (n=2), or prednisone (n=1). Nine patients were not treated with chemotherapy. The median age was 72 years (60-87). Of the 79 NHL patients, 65 were treated with CHOP chemotherapy (82%); 38 of 65 patients (59%) were adequately treated. The complete remission rate in the NHL group treated with CHOP was 65% (42 of 65 patients). The overall 3-year survival was 50%. Most of the patients died from progressive NHL (53% in the CHOP and 77% in the group not treated with CHOP). The treatment-related mortality was 15% in the CHOP group. The most important reason for not treating patients with CHOP (with or without G-CSF) was poor performance (WHO > or = 2). A significant subset of patients can be treated with CHOP chemotherapy with acceptable toxicity. The combination of CHOP plus G-CSF increased the absolute number of treatable elderly patients, resulting in more (absolute) patients with complete remission and overall survival compared to our previous study.

21
UI - 21420147
AU - Niitsu N; Iijima K; Chizuka A
TI - Combination therapy with irinotecan (CPT-11), mitoxantrone, and dexamethasone in relapsed or refractory non-Hodgkin's lymphoma: a pilot study.
SO - Ann Hematol 2001 Jul;80(7):411-6
AD - First Department of Internal Medicine, Toho University School of Medicine, Japan. nniitsu@med.kitasato-u.ac.jp
Irinotecan hydrochloride (CPT-11) is a topoisomerase I inhibitor with a broad antitumor spectrum. In the present study, we combined CPT-1 and mitoxantrone (MIT) with dexamethasone because the effect elicited by this combination was additive or better in a preclinical study. This study was performed to determine the efficacy and toxicities of this combination. Thirty-two patients were evaluable. CPT-11 combined with MIT achieved a complete remission in 11 patients (34.4%) and a partial remission in 9 patients (28.1%). The median follow-up period was 20 months. The 4-year survival rate was 31.8% (95% confidence intervals: 11.2-64.6%), and the 3-year event-free survival rate was 16.1% (95% confidence intervals: 8.2-24.6%). Grade 3 or higher hematological toxicity included neutropenia in 96.9%, anemia in 3.1%, and thrombocytopenia in 15.6%. Grades 1, 2, and 3 nonhematological toxicity included diarrhea in one patient, nausea/vomiting in five patients, and hematuria in one patient, respectively. CPT-11 combined with MIT was safe even for elderly patients and was effective even in patients who had received pretreatment with doxorubicin. In addition, this regimen can be used on an outpatient basis. This combination should be tested further to determine the optimum doses and administration schedule.

22
UI - 21400581
AU - Solaro C; Murialdo A; Giunti D; Mancardi G; Uccelli A
TI - Central and peripheral nervous system complications following allogeneic bone marrow transplantation.
SO - Eur J Neurol 2001 Jan;8(1):77-80
AD - Department of Neurological Sciences and Vision, University of Genoa, Italy. labunit@cisi.unige.it
Although graft vs. host disease (GvHD) is a frequent complication of allogeneic bone marrow transplantation (BMT), involvement of the central and peripheral nervous systems (CNS and PNS, respectively) has not been demonstrated conclusively. Here, we report of a patient who, following allogeneic BMT for lymphoblastic T-cell lymphoma, suffered a syndrome characterized by self-remitting cerebellar and pyramidal signs associated with a progressive involvement of the peripheral nervous system (PNS). Clinical course and laboratory findings correlated with relapses of systemic GvDH, thus suggesting the possibility that involvement of CNS and PNS may be sustained by a similar pathogenic mechanism.

23
UI - 21230829
AU - Kim WS; Song SY; Ahn YC; Ko YH; Baek CH; Kim DY; Yoon SS; Lee HG; Kang WK; Lee HJ; Park CH; Park K
TI - CHOP followed by involved field radiation: is it optimal for localized nasal natural killer/T-cell lymphoma?
SO - Ann Oncol 2001 Mar;12(3):349-52
AD - Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Ku, Seoul, Korea.
The present study aimed to analyse the treatment outcome of four cycles of CHOP (cyclophosphamide-vincristine-doxorubicin-prednisolone) followed by involved field radiation therapy (IF RT) for the treatment of stage I-II nasal natural killer (NK)/T-cell lymphoma. From March 1995 to December 1999, 17 patients (median age 41 years; range 30-66) with localized nasal NK/T-cell lymphoma were enrolled. B symptoms were noted in five patients (31%). Sixteen of seventeen patients (94%) were of low risk when classified according to the International Prognostic Index (IPI). The treatment plan consisted of four cycles of CHOP chemotherapy followed by IF RT of 45 Gy. Two patients received radiation during the first or second cycle of CHOP because of bleeding from the primary tumour site. Both patients achieved complete responses (CRs). In the remaining 15 patients, after 4 cycles of CHOP, 6 CRs and 3 partial responses (PRs) were achieved (53% of response rate). IF RT was given to six patients (four in CR, one in PR and one in PD), and all six patients achieved CR. Overall, CR was achieved in 10 of 17 patients (58%). The planned sequential chemoradiotherapy was completed in only 6 of 17 patients (35%) because of the progression during chemotherapy. None of the patients who achieved CR experienced relapse of lymphoma during follow-up. The estimated overall three-year survival rate was 59%. In univariate analysis, B symptoms and stage were significant prognostic factors for response and overall survival (P < 0.05). The present study suggests that four cycles of CHOP followed by IF RT is not satisfactory for treating patients with localized nasal NK/T-cell lymphoma, and that further exploration for improved therapy is needed.

24
UI - 21232936
AU - Genvresse I; Lange C; Schanz J; Schweigert M; Harder H; Possinger K; Spath-Schwalbe E
TI - Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.
SO - Anticancer Drugs 2001 Apr;12(4):345-9
AD - Internal Medicine II, Department Hematology/Oncology, Humboldt University, University Hospital Charite, 10117 Berlin, Germany. isabelle.genvresse@charite.de
In order to determine if age and comorbidity influence the tolerability of the cytoprotective agent amifostine, we compared side effects related to amifostine in patients > or = 70 years (group I) with patients < 70 years (group II). We evaluated 268 consecutive administrations of amifostine (119 in group I and 149 in group II, respectively), given i.v. at a dose of 740 mg/m(2) just before platinum-, taxol- or cyclophosphamide-based chemotherapy. Transient hypotension was the most common side effect occurring in association with amifostine. Decreases in systolic blood pressure > 20 mmHg were of similar frequency in both groups (27.1 versus 28.8% of amifostine infusions in group I and II, respectively). Hypotension did not result in medical sequelae in any of the patients. The amifostine infusion was interrupted 16 times in group I and 8 times in group II, respectively, mainly due to hypotension, but could be restarted after a few minutes in all patients except for three cases in group I. Patients in group II more often suffered from nausea/vomiting than in group II (20.8 versus 10.0% in group I). Other subjective symptoms (e.g. warmed, flushed sensation, sneezing, metallic taste, mouth dryness, dizziness and sleepiness) and hypocalcemia occurred with a similar frequency in both groups. Adverse effects associated with amifostine were not observed more frequently in elderly patients than in younger ones, although more elderly patients had a comorbidity than the younger ones.

25
UI - 21259865
AU - Aviles A; Leon MI; Diaz-Maqueo JC; Garcia EL; Cleto S; Neri N
TI - Rituximab in the treatment of refractory follicular lymphoma -- six doses are better than four.
SO - J Hematother Stem Cell Res 2001 Apr;10(2):313-6
AD - Research Unit in Oncology Diseases, National Medical Center, IMSS, Mexico, D.F. Mexico. a.aviles@infosel.net.mx
Seventeen patients with refractory follicular lymphoma heavily treated with chemotherapy (>2 regimens), radiotherapy, and biological modifiers were enrolled in a pilot study to receive six weekly doses, instead of the more frequent four doses, of monoclonal anti CD20, at a standard dose of 375 mg/m(2). In an intent-to-treat analysis, overall response was 76%, of which 47% (8 patients) were a complete response. With a median follow-up of 33.6 months, 7 complete responders remained alive and free of disease, and 2 partial-response patients remained stable without additional treatment. Actuarial curves showed that at 3 years, 53% of patients should be alive and free of disease. The 4 patients who were failures died secondary to tumor progression. Overall survival at 3 years was 76%. Toxicity was mild; all patients completed the schedule on time and doses. The addition of two doses of anti-CD 20 clearly improved the outcome in a group of patients with refractory follicular lymphoma heavily treated and poor prognostic factors. However, the number is too small to drawn definitive conclusions, and more clinical trials are necessary to determine if four of six doses of anti-CD20 therapy are better in this setting of patients.

26
UI - 21306025
AU - Brage A; Castroagudin J; Bustamante M; Abdulkader I; Perez-Encinas M
TI - [Primary liver lymphoma. Diagnostic and therapeutic implications]
SO - Gastroenterol Hepatol 2001 May;24(5):269-70

27
UI - 21391305
AU - Reno J
TI - My life as a guinea pig.
SO - Newsweek 2001 Aug 6;138(6):42

28
UI - 21384748
AU - Mandigers CM; Meijerink JP; Mensink EJ; Tonnissen EL; Hebeda KM; Bogman MJ; Raemaekers JM; Interzol (South-East Netherlands Comprehensive Cancer Centers Cooperative Group)
TI - Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma.
SO - Blood 2001 Aug 15;98(4):940-4
AD - Departments of Hematology and Pathology and the Central Hematology Laboratory, University Medical Center Nijmegen, The Netherlands.
In follicular lymphoma, the t(14;18) status of the peripheral blood and bone marrow analyzed by polymerase chain reaction (PCR) is assumed to correlate with disease activity in patients with relapsed disease. The clinical significance of quantitating circulating lymphoma cells by real-time PCR is reported in patients on first-line treatment. Thirty-four consecutive patients with previously untreated follicular lymphoma and detectable t(14;18)-positive cells in pretreatment peripheral blood samples were monitored. All patients were treated with standard chemotherapy in combination with interferon alfa-2b. Before and after induction therapy, blood samples were taken for quantitative analysis of t(14;18). At presentation, a median of 262 t(14;18)-positive cells per 75,000 normal cells was found (range, 1-75 000). Patients with lower numbers of circulating tumor cells more frequently had bulky disease (P =.02). Seventy-nine percent of the patients responded clinically to treatment. In 22 of 28 patients, including 4 patients in whom treatment had failed clinically, the number of circulating t(14;18)-positive cells decreased to undetectable or low levels after therapy. In the remaining responding patients, circulating tumor cells persisted after therapy. These quantitative data on circulating t(14;18)-positive cells call into question the usefulness of molecular monitoring of the blood in a group of patients with follicular lymphoma uniformly treated with a noncurative first-line regimen. T(14;18)-positive cells decreased in peripheral blood after treatment, irrespective of the clinical response. Therefore, the significance of so-called molecular remission should be reconsidered in follicular lymphoma. (Blood. 2001;98:940-944)

29
UI - 21424066
AU - Rodriguez J; Munsell M; Yazji S; Hagemeister FB; Younes A; Andersson B; Giralt S; Gajewski J; de Lima M; Couriel D; Romaguera J; Cabanillas FF; Champlin RE; Khouri IF
TI - Impact of high-dose chemotherapy on peripheral T-cell lymphomas.
SO - J Clin Oncol 2001 Sep 1;19(17):3766-70
AD - Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
PURPOSE: To evaluate the outcome of high-dose chemotherapy (HDCT) and autologous or allogeneic hematopoietic transplantation in patients with peripheral T-cell lymphoma (PTCL) who experienced disease recurrence after prior conventional chemotherapy. PATIENTS AND METHODS: We performed a retrospective analysis of 36 PTCL patients from the University of Texas M.D. Anderson Cancer Center treated between 1989 and 1998 with HDCT and autologous or allogeneic hematopoietic transplantation. RESULTS: A total of 36 patients were studied (29 received autologous transplantation, and seven received allogeneic transplantation). The overall survival rate at 3 years was 36% (95% confidence interval [CI], 23% to 59%), and the progression-free survival (PFS) rate was 28% (95% CI, 16% to 49%). The pretransplant serum lactate dehydrogenase level was the most important prognostic factor for both survival and PFS rates (P < .001). A Pretransplant International Prognostic Index score of < or = 1 indicated a superior survival rate (P = .036) but not an improved PFS rate. A median follow-up of 43 months (range, 13 to 126 months) showed 13 patients (36%) were still alive with no evidence of disease. CONCLUSION: Our results are comparable to the published data on HDCT in B-cell non-Hodgkin's lymphoma (NHL) patients despite the fact that patients with PTCL are known to have a worse outcome compared with B-cell NHL patients. Considering the dismal outcome of conventional chemotherapy in PTCL patients, these data suggest the hypothesis that the poor prognostic implication of T-cell phenotyping in NHL might be overcome by frontline HDCT and transplantation.

30
UI - 21319912
AU - Lefrere F; Hermine O; Francois S; Panelatti G; Valensi F; Grosbois B; Misset JL; Varet B; Troussard X
TI - Lack of efficacy of 2-chlorodeoxyadenoside in the treatment of splenic lymphoma with villous lymphocytes.
SO - Leuk Lymphoma 2000 Dec;40(1-2):113-7
AD - Service d'Hematologie Adultes, Hjpital Necker, Paris, France.
Splenic lymphoma with villous lymphocytes (SLVL) is a B-cell chronic lymphoproliferative disorder. Splenectomy and/or chlorambucil (CLB) are usually regarded as the most effective treatment in SLVL patients. However, a few patients relapse and the second line therapy remains questionable. Although 2-Cda has been evaluated in patients with chronic lymphoid leukemia (CLL) and hairy cell leuk

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