NCI CANCERLIT^® Search: Myeloproliferative Disorders - September 2001

Last Modified: November 1, 2001

Myeloid metaplasia of the breast.
The pathogenesis of chronic myeloproliferative diseases.
Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis.
Spontaneous regression of stage IV clear cell carcinoma of the endometrium in a patient with essential thrombocytosis.
Platelet apheresis for digital gangrene due to thrombocytosis in chronic myeloid leukaemia.
[Leukemic risk in thrombocythemia]
[Treatment of polycythemia. I--Using radiophosphorus with or without treatment in 483 patients over 65 years of age]
[Treatment of polycythemia. II.--Comparison of hydroxyurea with pipobroman in 294 patients less than 65 years of age]
K562 erythroleukemic cells are equipped with multiple mechanisms of resistance to lysis by complement.
Development of erythroleukaemia after myelodysplastic syndrome in a patient with Wegener's granulomatosis.

CancerMail from the National Cancer Institute

1
UI - 21193607
AU - Cufer T; Bracko M
TI - Myeloid metaplasia of the breast.
SO - Ann Oncol 2001 Feb;12(2):267-70
AD - Institute of Oncology, Ljubljana, Slovenia. tcufer@onko-i.si
Hereby, we present the case of a 50-year-old woman with 5-year history of chronic idiopathic myelofibrosis who was referred to our institution after she had noted a lump in the breast. Histological examination of the lesion removed from her left breast yielded the diagnosis of extramedullary hematopoiesis in the breast. On the basis of our experience in this particular patient and on the basis of the data in the literature, we discuss the value of different more or less invasive diagnostic procedures, such as sonography, mammography, fine needle aspiration biopsy and surgical excision with histological examination of removed tissue in obtaining the diagnosis of myeloid metaplasia in breast.

2
UI - 21265618
AU - Tefferi A
TI - The pathogenesis of chronic myeloproliferative diseases.
SO - Int J Hematol 2001 Feb;73(2):170-6
AD - Division of Hematology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. tefferi.ayalew@mayo.edu
Chronic myeloproliferative disorders are operationally classified to include essential thrombocythemia, polycythemia vera, and agnogenic myeloid metaplasia. In most cases, clonal hematopoiesis, involving all 3 myeloid lineages, can be demonstrated. However, the underlying molecular lesions that are responsible for disease initiation and progression remain elusive. There are ongoing efforts to clarify the pathogenetic role of cytokines, bone marrow stromal cells and molecules, and intracellular aberrations in either signal transduction or apoptosis. This review discusses some of the current and past observations regarding the pathogenesis of chronic myeloproliferative disorders.

3
UI - 21361154
AU - Anderson JE; Tefferi A; Craig F; Holmberg L; Chauncey T; Appelbaum FR; Guardiola P; Callander N; Freytes C; Gazitt Y; Razvillas B; Deeg HJ
TI - Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis.
SO - Blood 2001 Aug 1;98(3):586-93
AD - Division of Hematology, Department of Medicine, University of Texas Health Science Center at San Antonio, TX, USA.
Current therapeutic options for myeloid metaplasia with myelofibrosis (MMM) are limited. A pilot study was conducted of autologous peripheral blood stem cell (PBSC) collection in 27, followed by transplantation in 21 patients with MMM. The median age was 59 (range 45-75) years. PBSCs were mobilized at steady state (n = 2), after granulocyte colony-stimulating factor (G-CSF) alone (n = 17), or after anthracycline-cytarabine induction plus G-CSF (n = 8). A median of 11.6 x 10(6) (range 0 to 410 x 10(6)) CD34(+) cells per kilogram were collected. Twenty-one patients then underwent myeloablation with oral busulfan (16 mg/kg) and PBSC transplantation. The median times to neutrophil and platelet recovery after transplantation were 21 (range 10-96) and 21 (range, 13 to > or = 246) days, respectively. Five patients received back-up PBSC infusion because of delayed neutrophil or platelet recovery. The median follow-up is 390 (range 70-1623) days after transplantation, and the 2-year actuarial survival is 61%. After transplantion, 6 patients died: 3 of nonrelapse causes (1 within 100 days of PBSC infusion) and 3 of disease progression. Erythroid response (hemoglobin > or = 100 g/L [10 gm/dL] without transfusion for > or = 8 weeks) occurred in 10 of 17 anemic patients. Four of 8 patients with a platelet count less than 100 x 10(9)/L (100 000/microL) responded with a durable platelet count more than 100 x 10(9)/L (100 000/microL). Symptomatic splenomegaly improved in 7 of 10 patients. It is concluded that (1) PBSC collection was feasible and stable engraftment occurred after transplantation in most patients with MMM, (2) myeloablation with busulfan was associated with acceptable toxicity, (3) a significant proportion of patients derived clinical benefit after treatment, and (4) further investigation of this novel approach is warranted. (Blood. 2001;98:586-593)

4
UI - 21423720
AU - Parker R; Lanvin D; Gilks B; Miller D
TI - Spontaneous regression of stage IV clear cell carcinoma of the endometrium in a patient with essential thrombocytosis.
SO - Gynecol Oncol 2001 Aug;82(2):395-9
AD - Department of Pathology, Vancouver Hospital and British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 1M9, Canada.
OBJECTIVE: The aim of this study was to document a case of advanced stage clear cell carcinoma of the endometrium which underwent spontaneous regression (SR) and comment on the possible contribution of the patient's thrombocytosis. CASE REPORT: A 73-year-old woman with essential thrombocytosis presented with vaginal bleeding. Imaging demonstrated a complex uterine mass, a 4-cm infrarenal mass, and a 5-cm subumbilical mass. Biopsy of the subumbilical mass revealed adenocarcinoma, and endometrial curettage revealed extensively necrotic clear cell endometrial carcinoma. At hysterectomy 5 weeks later, the infrarenal and subumbilical masses were not identified. The endometrial tumor was almost completely necrotic. She received no adjuvant therapy and remains disease-free 6 years later. Interestingly, her platelet-lowering agent (hydroxyurea) was discontinued shortly before, and her platelet count was significantly elevated at the time of her presentation with endometrial carcinoma. CONCLUSION: This report documents a rare case of SR of advanced endometrial carcinoma, and we speculate that increased circulating platelets were a major contributing factor. Copyright 2001 Academic Press.

5
UI - 21315521
AU - Win N; Mitchell DC
TI - Platelet apheresis for digital gangrene due to thrombocytosis in chronic myeloid leukaemia.
SO - Clin Lab Haematol 2001 Feb;23(1):65-6
AD - National Blood Service - South London Centre, UK. Nay.Win@nbs.nhs.uk
Thrombocytosis is a frequent presenting feature of myeloproliferate disorders and is associated with increased incidence of thrombotic and haemorrhage complications. However, these complications are rare in chronic myeloid leukaemia (CML). We describe a case of CML which presented with digital gangrene due to thrombocytosis. Reduction of the platelet count by plateletpheresis lead to rapid symptomatic relief and recovery from the gangrene.

6
UI - 21383881
AU - Liozon E; Turlure P
TI - [Leukemic risk in thrombocythemia]
SO - Ann Med Interne (Paris) 1998 Mar;149(2):82-6
AD - Service de Medecine Interne A, CHRU Dupytren, 2, rue Martin-Luther-King, 87042 Limoges.
OBJECTIVES: To define pathogenesis, incidence, clinical presentation and prognosis of leukemic transformation (LT) in patients with essential thrombocytemia (ET); to compare the incidence of LT in previously treated versus untreated patients; to search for risk factors of LT, with special reference to the iatrogenic risk of myelosuppressive drugs. DATA SOURCES AND EXTRACTION: Most significant French and English-language papers published between 1981 and 1997 dealing with either ET, LT, clonality, cytogenetics, alkylating agents or hydroxyurea were reviewed. Patient characteristics, clinical presentation, bone marrow and cytogenetic findings, and survival data were extracted from each case report and review, and possible risk factors were analyzed. DATA SYNTHESIS: Despite the existence of clonal hematopoiesis in up to 60-80% of patients with ET, suggesting an intrinsic potential for subsequent leukemia, spontaneous LT is poorly documented and the common presumption that TL occurs in excess in treated patients with ET is still questionable. The incidence of LT, probably underestimated in the past, varies from 0.7% to 5.3% in retrospective series, and from 8% to 12% in prospective studies. Recurrent cytogenetic abnormalities are significantly more frequent and complex in marrow karyotypes performed at the time of blastic crisis, as compared with those performed at diagnosis. A review of 62 reports of LT highlights some important characteristics: a) LT can occur anytime during the chronic phase of ET, especially within the first eight years, b) all subtypes of leukemia are described, notably unclassifiable cases and megakary oblastic acute leukemias, c) bone marrow fibrosis is frequent, as is a progressive onset of a myelodysplastic syndrome preceeding the blastic crisis, d) the prognosis of LT is very poor, two-third of all patients die within 6 months. Apart from the onset of a myelodysplastic syndrome, which carries a poor outcome, there is no well-established risk factor of LT. The leukemogenic risk of myelosuppressive therapies, clearly demonstrated for years in polycythemia vera, cannot be directly ascertained in patients with ET, but is suggested by various indirect observations. This putative risk of inducing secondary leukemia affects not only alkylating agents but also hydroxyurea. CONCLUSION: LT is a highly serious and largely unpredictable complication of ET. The current debate on the specific risk of myelosuppressive treatments deserves large-scale prospective randomized studies. Until this crucial point is elucidated, any cytotoxic therapy should be reserved to elderly and/or symptomatic patients and to those having other vascular risk factors.

7
UI - 21383882
AU - Najean Y; Rain JD; Goguel A; Grange MJ; Vigneron N; Dupuy E; Mougeot-Martin M
TI - [Treatment of polycythemia. I--Using radiophosphorus with or without treatment in 483 patients over 65 years of age]
SO - Ann Med Interne (Paris) 1998 Mar;149(2):87-93
AD - Service de Medecine Nucleaire, Hopital Saint-Louis, 1 avenue Claude-Vellefaux, 75475 Paris.
AIMS: To compare by a prospective study in high risk polycythemia vera (PV) patients 33P alone and 32P followed by low-dose hydroxyurea (HU) maintenance therapy. Toxicity, efficiency, and leukemogenic potential were studied. PATIENTS: 483 patients with a documented PV, aged more than 65 years at diagnosis, were included between 1980 and 1996 in a prospective study comparing 32P alone and 32P followed by low-dose HU maintenance therapy. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months. RESULTS: Treatments were well tolerated, but chronic leg ulcers were observed in the maintenance therapy arm. The risk of leukemia was about 15% at the 15th year in the group of patients treated by 32P alone, but reached 30% in the group receiving maintenance therapy. In both arms, there was no significant correlation between occurrence of leukemia and the total dose of 32P. There was a correlation between the leukemic risk and disease severity, estimated on the frequency of relapse. Cancer occurrence was slightly higher than expected in the maintenance arm. HU treatment did not protect against progression to myelofibrosis, probably due to the lack of maintenance of an efficient myeloid or megakaryocytic suppression. Median life-span was slightly shorter in the group receiving HU maintenance. In all cases, life-span was only one year lower than that observed in the reference population. CONCLUSION: For all these reasons, we suggest the us of 32P alone in elderly patients; complementary chemotherapy should only be prescribed in the cases with short-term relapse, and late resistance to 32P.

8
UI - 21383883
AU - Najean Y; Rain JD; Lejeune F; Echard M; Fermand JP; Gruyer P; Brahimi S
TI - [Treatment of polycythemia. II.--Comparison of hydroxyurea with pipobroman in 294 patients less than 65 years of age]
SO - Ann Med Interne (Paris) 1998 Mar;149(2):94-100
AD - Service de Medecine Nucleaire, Hopital Saint-Louis, 1, avenue Claude-Vellefaux, 75475, Paris.
AIMS: To compare by a prospective study in low risk polycythemia vera (PV) patients alone two drugs: hydroxyurea and pipobroman. Toxicity, efficiency, and leukemogenic potential were studied. PATIENTS: 294 patients with a documented PV, aged less than 65 years, have been included since 1980 in a prospective study comparing hydroxyurea and pipobroman. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months. RESULTS: Hematologic toxicity of both drugs was higher than expected, requiring strict surveillance. These drugs were tolerated in some (gastric pain and diarrhea on pipobroman, buccal aphtosis and chronic leg ulcers on hydroxyurea), leading to a change of arm in 10% of the cases. Hydroxyurea did not control the megakaryocitic hyperplasia in 40% of the cases, which probably explains a high rate of progression to myelofibrosis with myeloid metaplasia in this arm. Both drugs were leukemogenic with an actuarial risk of about 15% at the 15th year, not significantly lower than that observed in the 32P treated patients. A significant risk of cutaneous malignancy was observed in the hydroxyurea arm. The mean expectancy of life cannot yet be accurately evaluated, but seems significantly lower than that of the reference population. CONCLUSION: The treatment of PV by hydroxyurea or pipobroman has to account for these results less optimistic than those traditionally well-known to hematologists and internists.

9
UI - 21409936
AU - Jurianz K; Ziegler S; Donin N; Reiter Y; Fishelson Z; Kirschfink M
TI - K562 erythroleukemic cells are equipped with multiple mechanisms of resistance to lysis by complement.
SO - Int J Cancer 2001 Sep15;93(6):848-54
AD - Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Resistance of tumor cells to lysis by complement is generally attributed to several protective mechanisms. The relative impact of these mechanisms in the same tumor cell, however, has not been assessed yet. We have analyzed the interaction of the human erythroleukemia tumor cell line K562 with human complement. K562 cells express the membrane complement regulatory proteins CD59, CD55 and CD46. As shown here for the first time, K562 also spontaneously release the soluble regulators C1 inhibitor, factor H, and soluble CD59. Complement resistance of K562 cells is augmented upon treatment with PMA, TNF or even with sublytic complement. Unlike TNF and sublytic complement, PMA enhanced the expression of membrane-bound CD55 and CD59 and led to increased secretion of soluble CD59. In addition, we show that complement-resistant K562 cells express a membrane-associated proteolytic activity, higher than the complement-sensitive K562/S cells. Treatment of complement-resistant K562 cells with serine protease inhibitors enhance their sensitivity to complement-mediated lysis. Inhibitors of protein kinase C (PKC) also sensitize K562 cells to complement lysis, implicating PKC-mediated signaling in cell resistance to complement. Neutralization of the CD55 and CD59 but not of CD46 regulatory activity with specific antibodies significantly increases complement-mediated K562 cell lysis. Treatment of K562 cells with a mixture of inhibitory reagents results in a significant additive enhancing effect on complement-mediated lysis of K562. In conclusion, K562 cells resist a complement attack by concomitantly using multiple molecular evasion strategies. Future attempts in antibody-based tumor therapy should include strategies to interfere with those resistance mechanisms. Copyright 2001 Wiley-Liss, Inc.

10
UI - 21425458
AU - Takaoka T; Matsukawa Y; Tomita Y; Kitamura N; Yamazaki T; Takeuchi J; Nishinarita S; Sawada U; Horie T
TI - Development of erythroleukaemia after myelodysplastic syndrome in a patient with Wegener's granulomatosis.
SO - Ann Rheum Dis 2001 Sep;60(9):899-900