melphalan and Primary-Myelofibrosis

The interrelation between plasma cell dyscrasia and myelofibrosis or agnogenic myeloid metaplasia (AMM) is unclear. The existence of two distinct syndromes has been proposed: (1) plasma cell dyscrasia associated with simple marrow fibrosis caused by the secretion of lymphokines and (2) myeloma coexisting with AMM representing two distinct clonal diseases.. The authors report the case of a 68 year-old man seen initially with severe anemia, massive splenomegaly, a leuko-erythroblastic blood morphology, and myelofibrosis coexisting with massive bone marrow infiltration with IgA lambda-producing plasmacytoid cells.. Cyclic therapy with vincristine, carmustine, cyclophosphamide, melphalan, and prednisone resulted in clinical remission of the myeloma lasting for 2 years and complete resolution of all the clinical features resembling AMM.. The authors' observations and the report of two other patients in whom remission of AMM has been observed after myeloma treatment underline the broad spectrum of secondary abnormalities ranging from moderate bone marrow fibrosis to the full clinical expression of a syndrome closely mimicking AMM. These secondary abnormalities are potentially reversible even in the presence of advanced bone marrow fibrosis and massive splenomegaly.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Diagnosis, Differential; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paraproteinemias; Prednisone; Primary Myelofibrosis; Splenomegaly; Vincristine

The role of spleen size and splenectomy for the prediction of post-allogeneic hematopoietic stem cell transplant (allo-HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000-2017 after either fludarabine-busulfan or fludarabine-melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000-2009 vs 14.1% in 2010-2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44-0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01-2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67-1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28-0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14-0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87-2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.

Topics: Allografts; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Disease-Free Survival; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Organ Size; Primary Myelofibrosis; Registries; Retrospective Studies; Spleen; Splenectomy; Survival Rate; Vidarabine

From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2(V617F) status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897.

Topics: Adult; Aged; Analysis of Variance; Antilymphocyte Serum; Blood Donors; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Janus Kinase 2; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Mutation; Primary Myelofibrosis; Prospective Studies; Siblings; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Unrelated Donors; Vidarabine

Although allogeneic hematopoietic stem cell transplantation has recently been applied to patients with myelofibrosis with reproducible engraftment and resolution of marrow fibrosis, no data describe the outcomes of umbilical cord blood transplantation. We describe 14 patients with primary (n = 1) and secondary myelofibrosis (n = 13) who underwent reduced-intensity umbilical cord blood transplantation. Conditioning regimens included fludarabine and graft-versus-host disease prophylaxis composed cyclosporine/tacrolimus alone (n = 6) or a combination of tacrolimus and mycophenolate mofetil (n = 8). Thirteen patients achieved neutrophil engraftment at a median of 23 days. The cumulative incidence of neutrophil and platelet engraftment was 92.9% at day 60 and 42.9% at day 100, respectively. Posttransplantation chimerism analysis showed full donor type in all patients at a median of 14 days. The use of umbilical cord blood could be feasible even for patients with severe marrow fibrosis, from the viewpoint of donor cell engraftment.

Topics: Aged; Busulfan; Cord Blood Stem Cell Transplantation; Feasibility Studies; Female; Graft Survival; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Primary Myelofibrosis; Radiotherapy Dosage; Remission Induction; Salvage Therapy; Survival Analysis; Transplantation Conditioning; Treatment Outcome; Vidarabine; Whole-Body Irradiation

Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7 months: 26 (26.3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40.4%) showed an improvement >50% (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28.4 and 26 months respectively: median survival of CR + PR patients was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the non-responders (log-rank test, P =0.002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR = 2.4) and not achieving any type of response, either partial or complete (HR = 3.9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Alkylating; Female; Follow-Up Studies; Humans; Leukocyte Count; Male; Melphalan; Middle Aged; Primary Myelofibrosis; Prognosis; Survival Rate; Treatment Outcome

Standard myeloablative conditioning prior to allogeneic hematopoietic stem cell (HSC) transplantation has been associated with significant toxicity in patients older than 45 years of age with myelofibrosis with myeloid metaplasia (MMM). We sought to evaluate the efficacy of a reduced-intensity conditioning regimen for allogeneic HSC transplantation in this setting. A regimen consisting of fludarabine (30 mg/m(2) intravenously daily for 5 days) and melphalan (70 mg/m(2) intravenously daily for 2 days) followed by transplantation of filgrastim-mobilized peripheral blood cells from HLA-identical siblings was administered to 4 older patients (median age, 56 years; range, 48-58 years) with advanced MMM. All patients achieved prompt neutrophil and platelet engraftment and have experienced a significant regression of splenomegaly and bone marrow fibrosis. All now have normal bone marrow cellularity. With a median follow-up of 13 months (range, 11-19 months), all 4 patients are alive with stable full-donor hematopoietic chimerism. These results support the feasibility and effectiveness of reduced-intensity conditioning prior to allogeneic HSC transplantation for older patients with advanced MMM.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Follow-Up Studies; Graft Survival; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Male; Melphalan; Middle Aged; Primary Myelofibrosis; Splenomegaly; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vidarabine

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) and inferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan. Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.

Topics: Adolescent; Adult; Busulfan; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Primary Myelofibrosis; Retrospective Studies; Transplantation Conditioning; Vidarabine

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.

Topics: Adult; Aged; Allografts; Busulfan; Disease-Free Survival; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Primary Myelofibrosis; Splenectomy; Survival Rate; Thiotepa; Transplantation Chimera; Transplantation Conditioning

The aim of this study is to compare clinical outcomes of patients who underwent allogeneic stem cell transplantation (HCT) for myelofibrosis with reduced intensity conditioning (RIC) using either Busulfan Fludarabine (BuFlu), Fludarabine Bis-chlorethyl-nitroso-urea/ carmustine Melphalan (FBM) or Fludarabine Melphalan (FluMel) regimens. Sixty-one patients were identified who underwent HCT with one of these RIC regimens. Overall survival (OS) was not different in the 3 groups. However, 100% donor chimerism was seen in more frequently at day +30 and day +100 in patients who received FBM or FluMel than BuFlu, in both CD3 and CD33 fractions. For instance, 100% donor chimerism in CD33 fraction was present in 100% patients in FBM cohort, 90% in FluMel cohort while 44% in BuFlu cohort at day +100. Acute graft-versus host disease, grade 2-4 and grade 3-4, was not statistically different in the 3 groups (BuFlu 47 and 35%, FBM 68 and 27%, FluMel 68 and 46%; p = 0.31 and 0.45). Relapses and non-relapse mortality was also not statistically significantly different. Our study shows similar OS with these 3 RIC regimens in myelofibrosis; although donor chimerism at day +30 and day +100 was better in patients who received FBM and FluMel.

Topics: Adult; Aged; Antineoplastic Agents; Busulfan; Carmustine; Chimerism; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Primary Myelofibrosis; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Topics: Adult; Aged; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Mutation; Primary Myelofibrosis; Prognosis; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Unrelated Donors; Vidarabine Phosphate

Topics: Aged; Antimetabolites, Antineoplastic; Azacitidine; Blast Crisis; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Male; Melphalan; Middle Aged; Mutation; Myeloproliferative Disorders; Pipobroman; Polycythemia Vera; Primary Myelofibrosis; Prognosis; Remission Induction; Retrospective Studies; Thrombocythemia, Essential; Treatment Outcome

Allogeneic hematopoietic stem cell transplantation remains the sole curative option for myelofibrosis. Many transplantation recipients receive a reduced-intensity conditioning (RIC) regimen owing to age or comorbidities; however, there is little published evidence to guide the choice of RIC regimen. In this study, we compared outcomes in patients who received 1 of 2 frequently used RIC regimens for patients with myelofibrosis: fludarabine-busulfan (FB) and fludarabine-melphalan (FM). A total of 160 patients underwent a RIC allograft procedure (FB group, n = 105; FM group, n = 55). We have developed a complex statistical model involving weighting and adjustment to permit comparison between these 2 groups. After weighting, the incidence of acute graft-versus-host disease (GVHD) was 62% in the FM group and 31% in the FB group (P = .001), and the corresponding incidence of chronic GVHD was 49% and 53%, respectively. The 7-year progression-free survival was were 52% in the FM group versus 33% in the FB group, and the 7-year overall survival rate 52% in the FM group versus 59% in the FB group. Nonrelapse mortality (NRM) was 43% in the FM group and 31% in the FB group. Multivariable analyses revealed no significant differences in PFS between the 2 groups; however, the relapse rate was significantly lower in the FM group (hazard ratio, 9.21; P = .008), whereas a trend toward reduced NRM was seen in the FB group (hazard ratio, 0.51; P = .068). In conclusion, both regimens appear to be efficient in mediating disease control and can be used to successfully condition patients with myelofibrosis. The FM regimen appears to induce more NRM than the FB regimen, but with augmented control of disease, leading to comparable overall survival rates for both regimens.

Topics: Aged; Busulfan; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Primary Myelofibrosis; Recurrence; Survival Analysis; Transplantation Conditioning; Treatment Outcome; Vidarabine

In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and non-myeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P=0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Calreticulin; Combined Modality Therapy; Cord Blood Stem Cell Transplantation; Cyclophosphamide; Disease Progression; Female; Graft Survival; Humans; Janus Kinase 2; Male; Melphalan; Middle Aged; Myeloablative Agonists; Neutrophils; Peripheral Blood Stem Cell Transplantation; Polycythemia Vera; Primary Myelofibrosis; Receptors, Thrombopoietin; Retrospective Studies; Thrombocythemia, Essential; Transplantation Conditioning; Treatment Outcome; Vidarabine; Whole-Body Irradiation; Young Adult

This sixteenth biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials (RCTs) in the field of hemato-oncology, with special focus on non-Hodgkin's lymphoma. The report covers the publication period June 2012 to July 2013. Trials are selected regarding their methodology and implication for clinical practice. Studies were identified by electronic search of MEDLINE using a broad search filter that covers all topics in hemato-oncology combined with a highly sensitive search filter for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). Four RCTs are presented in detail, followed by two further RCTs of high importance in a short version. The report is finalized with an overview of new and updated Cochrane Reviews.

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Boronic Acids; Bortezomib; Carmustine; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Etoposide; Hematologic Neoplasms; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Melphalan; Nitriles; Nitrogen Mustard Compounds; Prednisone; Primary Myelofibrosis; Pyrazines; Pyrazoles; Pyrimidines; Quality of Life; Randomized Controlled Trials as Topic; Rituximab; Vincristine

Leukemic transformation (LT) from myelofibrosis has a very poor prognosis with the current treatment strategies. We hypothesized that allogeneic stem cell transplantation (ASCT) can improve outcomes for patients with LT, and reviewed 55 consecutive patients that were treated for myelofibrosis with ASCT at our institution. Fourteen patients (25%) were identified to have LT. Thirteen of these patients received induction chemotherapy and 6 achieved remission at the time of transplant. Conditioning regimen was melphalan (Mel)-based in 9 patients. All patients engrafted and achieved remission after transplant, whereas 4 subsequently relapsed. After a median follow-up of 31 months, 6 patients (49%) survived long term. Although limited by a small number of patients, this study suggests that patients with myelofibrosis and LT may achieve long-term remission after induction chemotherapy and ASCT.

Topics: Aged; Cell Transformation, Neoplastic; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Melphalan; Middle Aged; Primary Myelofibrosis; Prognosis; Transplantation Conditioning; Treatment Outcome

A 60-year-old man was found to have anemia and leukocytosis from a health examination, and diagnosed with primary myelofibrosis (PMF). He was treated with low-dose melphalan but required frequent transfusions of red blood cells, and his splenomegaly enlarged. He received reduced-intensity stem cell transplantation (RIST)from an HLA-identical unrelated donor. The recovery of hematopoiesis was delayed due to the small number of transplanted cells (0.4 x 10(8)/kg). Splenomegaly and myelofibrosis gradually improved, and transfusion was not necessary 6 months later. He died of pneumonia about 1 year after transplantation. However, this case suggests that RIST is an effective treatment for PMF with giant splenomegaly.

Topics: Fatal Outcome; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Primary Myelofibrosis; Stem Cell Transplantation; Tomography, X-Ray Computed

Ten years after being diagnosed with polycythemia vera, a 55-year-old woman required frequent blood transfusion due to secondary myelofibrosis. She underwent reduced-intensity stem cell transplantation (RIST) from an HLA-identical sibling donor. Since mixed chimerae were identified in the peripheral blood at day 35, cyclosporine was withdrawn. At day 73, she developed acute graft-versus-host disease of the liver, while simultaneous resolution of splenomegaly occurred and complete donor chimerism in the peripheral blood was achieved. Frequent red blood cell transfusion was required until day 300 after transplantation. Thus, RIST for an older patient with secondary myelofibrosis was successful without severe treatment-related morbidity. This case suggests that RIST could be an effective treatment modality for secondary myelofibrosis.

Topics: Female; Graft vs Host Disease; Humans; Janus Kinase 2; Melphalan; Middle Aged; Polycythemia Vera; Primary Myelofibrosis; Stem Cell Transplantation; Transplantation Conditioning; Treatment Outcome; Vidarabine

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Female; Humans; Male; Melphalan; Middle Aged; Phenotype; Primary Myelofibrosis; Prognosis; Time Factors; Treatment Outcome

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Topics: Acute Disease; Anemia, Refractory, with Excess of Blasts; Busulfan; Cell Transformation, Neoplastic; Chlorambucil; Cohort Studies; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Hydroxyurea; Incidence; Interferon-alpha; Leukemia; Leukemia, Radiation-Induced; Male; Melphalan; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Preleukemia; Primary Myelofibrosis; Retrospective Studies; Ribonucleotide Reductases; Risk; Thrombocythemia, Essential

Leukemic transformation in essential thrombocythemia (ET) is rare. We describe a patient with ET which transformed to megakaryoblastic leukemia with myelofibrosis after treatment with melphalan for 8 years. His course after transformation smouldered for 20 months without antileukemic chemotherapy. A 61-year-old man was referred by a local doctor to Niigata University Hospital due to nasal bleeding in June 1984. Complete blood count (CBC) was as follows; hemoglobin 12.4 g/dl, platelets 268.8 x 10(4)/microliters, and white blood cells 11,900/microliters, with differentials of 39% PMN, 1% basophils, 2% eosinophils, 4% monocytes, and 13% lymphocytes. Bone marrow examination revealed hyperplasia of megakaryocytes without increase of reticulin fibers. Neutrophil alkaline phosphatase activity and karyotype of marrow cells were normal. ET was diagnosed. He was followed up by local doctor. The platelet count was controlled at a level of approximately 40 x 10(4)/microliters with melphalan for eight years. In January 1992 he developed pain in his lower extremities. He was admitted to our hospital on May 29, 1992. CBC was as follows; hemoglobin 8.9 g/dl, platelets 14.3 x 10(4)/microliters, and white blood cells 3,500/microliters, with differentials of 25% PMN, 5% monocytes, 28% lymphocytes, and 24% blasts. Bone marrow aspiration was unsuccessful and bone marrow biopsy revealed increases in fibroblasts and collagen fibers. Circulating blasts were positive for CD4, CD7, CD25, CD13, CD33, CD34, and HLA-DR and partly positive for CD41 and CD36. In ultrastructural cytochemistry blasts were positive for platelet peroxidase but negative for myeloperoxidase. Cytogenetic study revealed 46, XY, +der (1) t(1:7) (p11;q11) in all of five metaphases. He was diagnosed with megakaryoblastic leukemia accompanied by myelofibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blast Crisis; Humans; Leukemia, Megakaryoblastic, Acute; Male; Melphalan; Primary Myelofibrosis; Thrombocythemia, Essential

Topics: Alkylating Agents; Biopsy; Bone Marrow; Humans; Melphalan; Middle Aged; Multiple Myeloma; Prednisolone; Primary Myelofibrosis

Topics: Aged; Humans; Male; Melphalan; Multiple Myeloma; Primary Myelofibrosis

Topics: Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Primary Myelofibrosis

Topics: Aged; Female; Humans; Melphalan; Multiple Myeloma; Primary Myelofibrosis; Vincristine

The various myeloproliferative diseases have different symptoms, therapeutic problems, and prognoses. The most common of these disorders appears to be agnogenic myeloid metaplasia, which primarily affects older persons. The five-year survival rate at the Mayo Clinic for these patients is 58%, and the prognosis depends on the presence of symptoms, anemia, and thrombocytopenia and on the size of the liver. Androgen therapy is often necessary to control anemia, and splenectomy may be indicated.

Topics: Adult; Aged; Chlorambucil; Female; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential

Topics: Agammaglobulinemia; Antibodies; Antigens, Bacterial; Blood Protein Disorders; Blood Proteins; Busulfan; Chlorambucil; Electrophoresis, Paper; Hodgkin Disease; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulins; Immunosuppression Therapy; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Mannomustine; Melphalan; Primary Myelofibrosis; Radiation Effects; Saliva; Skin Tests; Spleen; Time Factors

Topics: Aged; Anemia, Sideroblastic; Blood Platelets; Female; Hemoglobinometry; Humans; Leukocyte Count; Leukopenia; Male; Melphalan; Polycythemia Vera; Primary Myelofibrosis