melphalan and Myeloproliferative-Disorders

Topics: 5-Aminolevulinate Synthetase; Adult; Anemia, Sideroblastic; Blood Transfusion; Bone Marrow; Chloramphenicol; Deferoxamine; Erythroblasts; Ethanol; Female; Ferrochelatase; Heme; Hemochromatosis; Humans; Iron Deficiencies; Isoniazid; Male; Melphalan; Myeloproliferative Disorders; Pyridoxine; Syndrome

To evaluate melphalan instead of cyclophosphamide in modified busulfancyclophosphamide regimen as a new myeloablative conditioning regimen for the treatment of myeloid malignancies patients receiving allogeneic hematopoietic stem cell transplantation （HSCT）.. The clinic data of 94 myeloid malignancies patients undergoing allogeneic HSCT were analyzed, of which 48 patients received Bu+Cy+Flu+Ara-C, 46 cases Bu+Mel+Flu+Ara-C regimens. Rregimen-related toxicity, engraftment, graft- versus-host disease（GVHD）, infection condition, non- relapse mortality, and overall survival were compared between the two groups.. All patients achieved neutrophil engraftment. The incidence of grade Ⅲ-Ⅳ oral mucositis and diarrhea in BMFA group was higher than in BCFA group（P<0.05）. The incidence of acute GVHD in BMFA group was also higher than in BCFA group but without statistically significant difference（36.5% over 56.5%, P=0.100）. With a median follow up of 42 months, the incidence of no relapse mortality in BCFA group was 12.5% and 19.6% in BMFA group（P=0.400）. The relapse rate in BMFA group（4.3%）was significantly lower than in BCFA group （25.0%, P=0.009）. The overall survival rates were（71.8±6.7）% and（76.1±6.3）%（P=0.852）, and diseasefree survival rates were（67.8±8.9）% and（76.1±6.3）%（P=0.567）were comparable between BCFA group and BMFA group.. Melphalan instead of cyclophosphamide as a new myeloablative conditioning regimen had lower relapse and satisfied disease-free survival rates, but the risk of regimenrelated toxicity and GVHD should be taken into consideration.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Myeloproliferative Disorders; Neoplasm Recurrence, Local; Remission Induction; Survival Rate; Transplantation Conditioning; Transplantation, Homologous

Myeloablative conditioning followed by T-cell depletion of grafts and reduced intensity conditioning (RIC) has both been shown to decrease treatment related mortality (TRM). However in RIC the incidence of graft vs. host disease (GvHD) is high and patients with aggressive diseases tend to relapse. Following myeloablative conditioning, patients with chemotherapy-responsive hematological malignancies underwent transplantation from HLA identical siblings. GvHD prophylaxis was by ex viva T-cell depletion with alemtuzumab. The outcome of these patients was analysed. At transplantation, the median age of 81 consecutive individuals was 45 years (range 15-60). GvHD was seen in 10% and was commonly associated with infections resulting in one and 3 year TRM of 15 and 20.5%. Fifteen patients relapsed, 10 who had myeloproliferative syndromes or lymphoma and two with myeloma responded to DLI. For the whole group, median follow up is 777 (range 7-2702) days and 73% remain disease free. Cox regression analysis for survival showed that only occurrence of GvHD was a significant adverse factor. Age order than median was not associated with worse outcome. By reducing the incidence and severity of GvHD, T-cell depletion of grafts leads to greater tolerance to myeloablative chemotherapy, resulting in acceptable TRM. This strategy should be compared with the RIC approaches.

Topics: Adolescent; Adult; Alemtuzumab; Antibiotic Prophylaxis; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Busulfan; Cyclophosphamide; Female; Graft vs Host Disease; Hematologic Neoplasms; Humans; Lymphocyte Depletion; Male; Melphalan; Myeloablative Agonists; Myelodysplastic Syndromes; Myeloproliferative Disorders; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Risk; Survival Analysis; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous; Whole-Body Irradiation

In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Administration Schedule; Epirubicin; Female; Humans; Interferon alpha-2; Interferon-alpha; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloproliferative Disorders; Peptichemio; Prednisone; Recombinant Proteins; Vincristine

Thirty-one patients with essential thrombocythemia were randomized to receive either melphalan or radioactive phosphorus as myelosuppressive therapy. Twenty-seven patients were evaluable for response. Of 13 patients treated with melphalan, 11 had a complete response (platelet count less than 450,000/mm3) at 3 and 6 months. This response rate was significantly better than the response to radioactive phosphorus. The response rates were similar at 12 months. No significant toxicity was observed with either regimen.

Topics: Aged; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocythemia, Essential

Allogeneic hematopoietic cell transplantation (alloHCT) remains the only curative option for relapsed/refractory acute myeloid leukemia and other high-risk myeloid malignancies. To improve alloHCT results in this setting, sequential regimens were designed as a strategy to lower tumor burden and quickly induce the graft-versus-leukemia effect. We analyzed long-term outcomes of a sequential regimen based on IDA-FLAG and high-dose melphalan, as set forth by the CETLAM cooperative group. This protocol yielded a high complete response rate (89%) and a lower cumulative relapse incidence (30% at five years) compared to other regimens. Five-year non-relapse mortality, however, reached 45%, with grade 3-4 acute graft-versus-host disease being the most frequent adverse event (a 100-day incidence of 29%). Altogether, 5-year overall survival was 25% in this group of patients with otherwise dismal prognosis. Long-term survivors enjoyed a good quality of life after a median follow-up of 68 months.

Topics: Disease-Free Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Melphalan; Myeloproliferative Disorders; Quality of Life; Recurrence; Retrospective Studies; Transplantation Conditioning

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

Busulfan, fludarabine, and melphalan as hematopoietic cell transplant conditioning, was used in 6 patients aged 1 to 19 years with very high-risk myeloid malignancies. This dose regimen had an acceptable toxicity profile resulting in complete donor engraftment even following transplantation of small 2/6 antigen disparate umbilical cord blood grafts. It provided excellent disease control as all patients had high-risk features in terms of cytogenetics, therapy-related leukemia, and/or significant measurable disease before transplant. All patients remain in remission, without acute or chronic graft-versus-host disease with a median follow-up of 24 months. A larger study is indicated to confirm the efficacy and safety of this regimen.

Topics: Adolescent; Busulfan; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myeloid; Male; Melphalan; Myeloablative Agonists; Myeloproliferative Disorders; Remission Induction; Tissue Donors; Transplantation Conditioning; Treatment Outcome; Vidarabine; Young Adult

We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chromosome Aberrations; Chromosomes, Human, Pair 5; Chromosomes, Human, Pair 7; Cyclophosphamide; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Melphalan; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Myeloid Cells; Myeloproliferative Disorders; Neoplasms, Second Primary; Retrospective Studies

Mini-BEAM and ESHAP are two non-cross-resistant salvage regimens that have been used separately in patients with lymphoma. The aim of the present study was to investigate the efficacy of the combination of these two regimens, administered in alternating cycles, as salvage therapy for refractory non-Hodgkin's lymphoma (NHL) patients. A total of 28 patients were included in the study: 14 patients were primary refractory, seven were partial responders, and seven were in relapse. The alternating cycles of mini-BEAM and ESHAP were given until there was maximum response or progression. The overall response rate to mini-BEAM/ESHAP was 39%; 25% of patients achieved a complete response and 14% a partial response. Nevertheless, it should be noted that none of the primary refractory patients responded to this protocol. Nine of the 11 patients who responded to mini-BEAM/ESHAP were consolidated with autologous transplantation using BEAM as a conditioning regimen. The survival at 3 years in this group of 11 patients who responded to the salvage regimen is 64%, with a disease-free survival of 67% at 2 years. No major toxic effects were observed with mini-BEAM/ESHAP. Myelosuppression was the most frequent complication, especially with the mini-BEAM cycles. Other toxicities were infrequent and no treatment-related deaths were observed. These results suggest that alternating mini-BEAM/ESHAP chemotherapy is a safe regimen that is effective in partial responders or relapsing patients with NHL who have sensitive disease, but not in primary refractory patients. Moreover, although this therapy has a potential advantage, combining as it does two non-cross-resistant regimens, it does not seem superior to ESHAP alone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cisplatin; Cytarabine; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Methylprednisolone; Middle Aged; Myeloproliferative Disorders; Neutropenia; Salvage Therapy; Survival Rate; Time Factors

A 47-year-old woman developed a unique myeloproliferative disorder 36 months after receiving adjuvant chemotherapy postoperatively for breast carcinoma. Her bone marrow and peripheral blood exhibited many of the myelodysplastic changes commonly observed in treatment-linked leukemia. In addition, there was striking marrow and blood eosinophilia and eosinophilic infiltration in multiple organs. She also developed a poorly differentiated lymphocytic lymphoma which responded to therapy. Her myeloproliferative disorder, with marked eosinophilia, continued to progress, however, and she died shortly after its diagnosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Eosinophilia; Female; Humans; Lymphoma, Non-Hodgkin; Mastectomy; Melphalan; Middle Aged; Myeloproliferative Disorders; Prednisone; Vincristine

Seventeen patients were treated with high-dose melphalan with autologous bone marrow transplant (ABMT) and cyclophosphamide pretreatment. All of the patients had marrow reconstitution. Although there was one death caused by infection, high-dose melphalan with ABMT causes toxicity that is generally acceptable, and can achieve a high-response rate, but with responses of short duration in tumors resistant to standard-dose combination chemotherapy. In other poor-prognosis tumors that are sensitive to chemotherapy, or can be debulked surgically, or locally irradiated, high-dose melphalan with ABMT given as late intensification therapy may significantly prolong time to relapse, and ultimately prolong survival.

Topics: Adult; Bacterial Infections; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Neoplasms; Prognosis; Vomiting

A case of myelodysplasia (refractory anaemia with excessive blasts) arising 7 years after a 3 year period of intermittent monthly treatment cycles with melphalan for multiple myelomas is reported. This is another example of preleukaemic syndrome possibly caused by melphalan. Among the possible pathogenetic mechanisms, the incidence of cyclic episodes of medullary hypoplasia are emphasised.

Topics: Blood Transfusion; Erythrocyte Transfusion; Female; Humans; Melphalan; Middle Aged; Multiple Myeloma; Myeloproliferative Disorders; Platelet Transfusion; Prednisone; Preleukemia; Time Factors

Topics: Adult; Drug Therapy, Combination; Female; Humans; Hyperthermia, Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Myeloproliferative Disorders; Plasmacytoma; Pyrogens; Radiotherapy Dosage; Sarcoma, Ewing

The effusive form of feline infectious peritonitis was diagnosed clinically and serologically in a 3-year-old male domestic cat. The cat responded to treatment for 9 months, then developed a myeloproliferative disorder with cytologic characteristics of reticuloendotheliosis.

Topics: Ampicillin; Animals; Cat Diseases; Cats; Male; Melphalan; Myeloproliferative Disorders; Peritonitis; Prednisone; Virus Diseases

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: Bone Diseases; Calcium; Female; Humans; Male; Melphalan; Myeloproliferative Disorders; Nitrogen Mustard Compounds; Pain