melphalan and Blast-Crisis

Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution.. Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy.. A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years.. EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Agents; Blast Crisis; Bone Marrow; Busulfan; Child; Cyclophosphamide; Etoposide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Lymphatic Irradiation; Melphalan; Middle Aged; Myelodysplastic Syndromes; Organ Sparing Treatments; Organs at Risk; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Radiotherapy Dosage; Recurrence; Transplantation Conditioning; Vidarabine; Whole-Body Irradiation; Young Adult

Six patients with either acceleration or blast crisis of transformed chronic myeloid leukemia (CML) were treated with high-dose interferon alpha in combination with hydroxyurea. All patients responded to the treatment by reversal to stable chronic phase. Two of these patients responded repeatedly during their course of disease. Median time for return to chronic phase was 4 weeks. Adverse side-effects such as nausea, vomiting, hairloss, fever, prolonged cytopenia were not observed.

Topics: Acetaminophen; Adult; Aged; Analgesics, Non-Narcotic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Cytarabine; Humans; Hydroxyurea; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Melphalan; Middle Aged

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

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

Autologous blood stem cell transplantation (ASCT) was performed in 32 patients with high risk chronic myelogenous leukemia (CML). Prior to ASCT, the patients were given Busulfan and high-dose Melphalan. Peripheral blood stem cells collected at diagnosis were used to rescue hematopoiesis. Recombinant Interferon was administered after ASCT. In 24 patients transplanted in transformation, 23 achieved a complete hematological response and nine are still alive 9 to 73 months after ASCT. Eight other patients were transplanted in chronic phase for either the presence of bad prognostic factors (Sokal's classification) or no response to IFN. Seven are alive without transformation 16 to 48 months after ASCT. Although few patients presented a cytogenetical response (10/28), the survival observed in this series of patients compares favorably with that of patients treated conventionally. Thus, the place of ASCT in CML could now be tested prospectively.

Topics: Adult; Blast Crisis; Blood Component Transfusion; Blood Transfusion, Autologous; Bone Marrow Purging; Busulfan; Combined Modality Therapy; France; Humans; Immunologic Factors; Interferon Type I; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Melphalan; Middle Aged; Prognosis; Recombinant Proteins; Risk; Survival Analysis; Treatment Outcome