National Cancer Institute®
Last Modified: June 1, 2002
UI - 11999364
AU - Tomonari A; Iseki T; Ooi J; Nagayama H; Sato H; Takahashi T; Ito K;
TI - Nagamura F; Uchimaru K; Takahashi S; Shirafuji N; Tojo A; Tani K; Asano S Second allogeneic hematopoietic stem cell transplantation for leukemia relapse after first allogeneic transplantation: outcome of 16 patients in a single institution.
SO - Int J Hematol 2002 Apr;75(3):318-23
AD - Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Japan. email@example.com
Sixteen patients who underwent a second allogeneic hematopoietic stem cell transplantation (HSCT2) for leukemia relapse after the first allogeneic transplantation (HSCT1) were studied. The patients included 7 patients with acute myelogenous leukemia, 8 with acute lymphoblastic leukemia, and 1 with chronic myelogenous leukemia. The median patient age at HSCT2 was 22 years (range, 12 to 44 years). The median interval between HSCT1 and HSCT2 was 19 months (range, 2 to 46 months). At HSCT2, 7 patients were in complete remission (CR), 7 had relapsed, and 2 had bone marrow aplasia. In 14 patients, donors for HSCT2 were the same as those for HSCT1. Two donors were replaced, 1 for another HLA-matched sibling and 1 for an unrelated cord blood donor. Four patients (25%) died within 100 days after HSCT2 from veno-occlusive disease, sepsis, interstitial pneumonitis, or chronic graft-versus-host disease (GVHD), without leukemia relapse. Seven patients (44%) developed leukemia relapse and died between 4 and 20 months after HSCT2. Five patients (31%) survived beyond 4 years. One patient died from chronic GVHD without leukemia relapse 55 months after HSCT2. The 4 other patients were alive between 79 and 134 months after HSCT2 (median follow-up, 106 months). Factors that favorably influenced survival were age younger than 20 years and CR duration after HSCT1 longer than 12 months. HSCT2 is considered to be beneficial for select patients. Preparative regimens, GVHD prophylaxis, and donor choice for HSCT2 need to be studied to obtain a more successful outcome for HSCT2.
UI - 11999366
AU - Saito T; Shinagawa K; Takenaka K; Matsuo K; Yoshino T; Kiura K; Niiya K;
TI - Harada M Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation.
SO - Int J Hematol 2002 Apr;75(3):332-4
AD - Second Department of Internal Medicine, Okayama University Medical School, Japan.
A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. Eighteen days after transplantation, the patient developed grade II acute graft-versus-host disease (GVHD) and was treated with corticosteroids. On day 38, the patient complained of eye pain and lacrimation. A slitlamp examination revealed corneal ulcers and pseudomembranous formation in both eyes. Histologic and immunohistochemical examinations of the pseudomembrane disclosed an infiltrate dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence in situ hybridization identified a Y chromosome in the infiltrated mononuclear cells. Surveillance cultures from conjunctival swabs were negative. Thus, we diagnosed these ocular manifestations as an ocular involvement of acute GVHD.
UI - 11902306
AU - Huang FS; Zwerdling T; Stern LE; Ballard ET; Warner BW
TI - Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia.
SO - J Pediatr Hematol Oncol 2001 Dec;23(9):609-11
AD - Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Numerous children have been treated successfully for cancer and are surviving into adulthood. As this population has aged, an increasing number of secondary malignancies has emerged. Renal cell carcinoma (RCC) is a rare tumor in childhood and has not been documented previously to occur after treatment of acute promyelocytic leukemia (APL). This report describes the clinical course of APL treated in a child in whom RCC subsequently developed during adolescence approximately 5 years after therapy.
UI - 11911247
AU - Faderl S; Estrov Z; Kantarjian HM; Harris D; Van Q; Fokt I; Przewloka T;
TI - Godlewski C; Woynarowski JM; Priebe W WP744, a novel anthracycline with enhanced proapoptotic and antileukemic activity.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3777-84
AD - The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
BACKGROUND: MDR1 or MRP1 drug resistance mechanisms seriously limit the efficacy of anthracyclines such as doxorubicin, in the treatment of acute myeloid leukemia (AML). Our studies indicated that reducing basicity, increasing steric hindrance at C-4', and/or lipophilicity may help circumvent P-glycoprotein (P-gp)-mediated anthracycline efflux and thus increase drug retention in MDR-positive cells. From a series of 4'-substituted analogs, 4'-O-benzylated doxorubicin (WP744) was selected for a comparison with the classic anthracycline doxorubicin for their cytotoxic and pro-apoptotic properties. WP744 retains cytotoxic activity against P-gp and MRP-positive cells. METHODS AND RESULTS: In three AML cell lines (K562, KBM-3, and OCIM2) WP744 was markedly more potent (IC50 values of 0.18, <0.05, and <0.05 microg/ml, respectively) than doxorubicin (IC50 values of >0.5, 0.07, and 0.09 microg/ml, respectively). Likewise, WP744 inhibited the colony formation by AML-CFU cells from fresh bone marrow of three AML patients more strongly than doxorubicin. Cell growth inhibition by WP744 is accompanied by apoptosis induction as shown by TUNEL assay in OCIM2 cells. WP744-induced apoptosis appears to be mediated by caspase-3 as apoptotic changes were abrogated in the presence of the caspase 3 inhibitor Z-DEVD-FMK. Accordingly, caspase 3 activity was elevated in the lysates from drug-treated cells. WP744 induced also cleavage of apoptotic marker poly(ADP-ribose)polymerase (PARP). Finally, WP744 at 0.05 microM and greater was a potent inducer of apoptosis (by quantitative DNA fragmentation) in cultured human acute lymphoblastic leukemia (ALL) CEM cells, compared to 0.5 microM doxorubicin needed for a similar effect. CONCLUSION: The novel anthracycline WP744 was found to be an antileukemic agent with proapoptotic activity superior to that of doxorubicin.
UI - 11732869
AU - Voog E; Le QH; Philip I; Benetaib B; Michallet M; Fiere D; Thomas X
TI - Autologous transplantation in acute myeloid leukemia: peripheral blood stem cell harvest after mobilization in steady state by granulocyte colony-stimulating factor alone.
SO - Ann Hematol 2001 Oct;80(10):584-91
AD - Service d'Hematologie, Hopital E. Herriot, Lyon, France.
In order to determine whether granulocyte colony-stimulating factor (G-CSF) alone initiated during steady state was able to mobilize peripheral blood stem cells (PBSC) in acute myeloid leukemia (AML) and to assess predictive factors for engraftment after autologous PBSC transplantation, we studied 49 successive adult AML patients for whom 1998. G-CSF was used as priming agent and was initiated at least 4 weeks after the last day of chemotherapy, while neutrophil count was >0.5 x 10(9)/l and platelet count was >30 x 10(9)/l. A median of three aphereses was performed resulting in a median collection of 14.8 x 10(8) nucleated cells/kg containing 7.7 x 10(8) mononuclear cells/kg, 47.1 x 10(4) CFU-GM/kg, and 3.8 x 10(6) CD34+ cells/kg. A significant correlation was observed between nucleated cell, mononuclear cell, and CFU-GM yields, while no correlation was found with CD34+ cell yield. Recruitment was not significantly different in patients with CD34+ leukemic cells at the time of initial diagnosis when compared to that of those presenting with CD34- blastic cells. Thirty-three patients actually underwent transplantation. Reasons for not autografting were inadequate stem cell harvest (ten patients), early relapse (two patients), prolonged neutropenia (one patient), organ failure (two patients), or patient refusal (one patient). Median time to achieve a neutrophil count greater than 0.5 x 10(9)/l and platelet count >50 x 10(9)/l untransfused was 13 and 36 days, respectively. A predictive factor for a shorter period neutropenia and a shorter thrombopenia was a higher count of harvested nucleated cells (p < 0.01 and p = 0.02, respectively). A higher count of harvested cells was also a predictive factor for less red cell and platelet transfusions (p=0.03 and p=0.02, respectively). The number of CD34+ harvested PBSC was not predictive for engraftment. We conclude that PBSC mobilization with G-CSF alone initiated in steady state is a feasible, safe, and suitable procedure for harvesting cells in sight of autologous transplantation in adult acute myeloid leukemia.
UI - 10942230
AU - Lengfelder E; Reichert A; Schoch C; Haase D; Haferlach T; Loffler H;
TI - Staib P; Heyll A; Seifarth W; Saussele S; Fonatsch C; Gassmann W; Ludwig WD; Hochhaus A; Beelen D; Aul C; Sauerland MC; Heinecke A; Hehlmann R; Wormann B; Hiddemann W; Buchner T Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group.
SO - Leukemia 2000 Aug;14(8):1362-70
AD - III. Medizinische Klinik Mannheim, University of Heidelberg, Germany.
A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy. Fifty-one patients, diagnosed and age was 43 (16-60) years. The morphologic diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients the initial white blood cell counts were > or =5 x 10(9)/l. The cytogenetic or molecular proof of the translocation t(15;17) was a mandatory prerequisite for eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of the PML/RARalpha transcript in 45 cases. The rate of complete hematological remission was 92% and the early death rate 8%. Monitoring of minimal residual disease by RT-PCR of PML/RARalpha (sensitivity 10(-4)) showed negativity in 29 of 32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18 months after diagnosis, respectively. After a median follow-up of 27 months, the estimated actuarial 2 years overall and event-free survival were both 88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic efficacy of this treatment strategy is demonstrated by a rapid and extensive reduction of the malignant clone and by a low relapse rate. The results suggest that the intensity of the induction chemotherapy combined with ATRA is one of the factors which may have a critical influence on the outcome of APL. A randomized trial should assess the value of an induction therapy including ATRA and high-dose ara-C in comparison to standard-dose ara-C.
UI - 11753627
AU - Sanz MA; Martin G; Rayon C; Deben G; Tormo M; Diaz-Mediavilla J; Esteve
TI - J; Gonzalez-San Miguel JD; Spanish PETHEMA Cooperative Group Uncertain role of increased intensity chemotherapy with high-dose cytarabine in acute promyelocytic leukemia.
SO - Leukemia 2001 Dec;15(12):1999-2002
UI - 11964275
AU - Lu DP; Qiu JY; Jiang B; Wang Q; Liu KY; Liu YR; Chen SS
TI - Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: a pilot report.
SO - Blood 2002 May 1;99(9):3136-43
AD - Peking University Institute of Hematology and People's Hospital, Beijing, China.
In the past 6 years, we treated 129 patients who had acute promyelocytic leukemia (APL) with a new arsenic agent, oral tetra-arsenic tetra-sulfide (As(4)S(4)). Nineteen of the patients had newly diagnosed APL, 7 had first relapse, and 103 had hematologic complete remission (HCR). HCR was achieved in all patients with newly diagnosed APL and in all those with hematologic relapse. Of 16 patients with newly diagnosed disease and available cytogenetic and molecular analyses, 14 had cytogenetic and molecular complete remission (CR). Cytogenetic and molecular CR was also obtained in 5 of the 7 patients with hematologic relapse. In the HCR group, 35 of 44 patients positive for PML-RARalpha at baseline became negative. In the newly diagnosed group, estimated disease-free survival (DFS) rates for 1 and 3 years were 86.1% and 76.6%, respectively, with a median follow-up time of 13.5 months (range, 2-40 months). In the HCR group, DFS rates for 1 and 6 years were 96.7% and 87.4%, respectively, with a median follow-up of 23 months (range, 2-71 months). Treatment with As(4)S(4) was well tolerated, with only moderate side effects, including asymptomatic prolongation of corrected QT interval, transient elevation in liver enzyme levels, rash, and mild gastrointestinal discomfort; neither myelosuppression nor appreciable long-term side effects occurred. Degeneration or apoptosis of APL promyelocytes was observed during As(4)S(4) therapy. Pharmacokinetic studies showed that the agent was absorbed rapidly. Most urinary arsenic excretion occurred within the first 24 hours. Both blood and urinary arsenic levels declined after discontinuation of As(4)S(4). Our results show, for the first time, that As(4)S(4) treatment alone is highly effective and safe in both remission induction and maintenance therapy in patients with APL, regardless of disease stage.
UI - 12040454
AU - Ashihara E; Shimazaki C; Takahashi R; Fuchida S; Ochiai N; Inaba T;
TI - Nakagawa M Mydriasis after the treatment of vindesine in a patient with acute promyelocytic leukemia.
SO - Leukemia 2002 Jun;16(6):1200
UI - 12017297
AU - Styczynski J; Wysocki M; Kurylak A; Juraszewska E; Malinowska I;
TI - Stanczak E; Ploszynska A; Stefaniak J; Mazur B; Szczepanski T; Ras M In vitro activity of glufosfamide in childhood acute leukemia.
SO - Anticancer Res 2002 Jan-Feb;22(1A):247-50
AD - Katedra i Klinika Pediatrii, Hematologii i Onkologii, Bydgoszcz, Poland. firstname.lastname@example.org
Glufosfamide is a new agent for cancer chemotherapy. The objective of the study was the comparison of the in vitro drug resistance profile of glufosfamide with other oxazaphosphorines in 106 samples of childhood acute leukemia by means of the MTT assay. The following drugs were tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide, mafosfamide cyclohexylamine salt, prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine. In the group of initial Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In comparison to initial ALL samples, the relative resistance for glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9 (p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML) samples, respectively, 31 (p<0.001) and 5 (p=0.001). All oxazaphosphorines showed highly significant cross-resistance. In conclusion, in vitro activity of glufosfamide is comparable to ifosfamide. Glufosfamide shows high activity against lymphoblasts both on diagnosis and on relapse, however it cannot circumvent resistance to other oxazaphosphorines.
UI - 2115958
AU - Rhodes AM
TI - A minor's refusal of treatment.
SO - MCN Am J Matern Child Nurs 1990 Jul-Aug;15(4):261
AD - Finance and University Services, University of Iowa, Iowa City.
UI - 12068383
AU - Atkins MB
TI - Interleukin-2: clinical applications.
SO - Semin Oncol 2002 Jun;29(3 Suppl 7):12-7
AD - Cutaneous Oncology & Biologic Therapy Programs, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Interleukin-2 (IL-2) is a promising immunotherapeutic agent for the treatment of metastatic melanoma, acute myelogenous leukemia, and metastatic renal cell carcinoma. While high-dose IL-2 regimens have shown clinical benefit in the treatment of melanoma and renal cell carcinoma, serious dose-limiting toxicities have limited their clinical use in a broader group of patients. Low-dose IL-2 therapy has produced disappointing clinical response rates in melanoma. While the response rates to low-dose IL-2 have been better in renal cell carcinoma, the quality of these responses relative to those seen with high-dose IL-2 therapy remains a concern. The addition of IL-2 to chemotherapeutic regimens (biochemotherapy) has been associated with overall response rates of up to 60% in patients with metastatic melanoma, but this has yet to be translated into a confirmed improvement in survival. It remains to be determined whether further modifications of IL-2-based regimens or the addition of newer agents to IL-2 will produce better tumor response and survival. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11920282
AU - Abou Chacra L; Ghosn M; Ghayad E; Honein K
TI - A case of pancreatitis associated with all-trans-retinoic acid therapy in acute promyelocytic leukemia.
SO - Hematol J 2001;2(6):406-7
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