mercaptopurine and Blast-Crisis

Acute myelofibrosis (AMF), as defined by an acute panmyelopathy associated with marked megakaryocytic hyperplasia and marrow fibrosis, appears to be a stem cell disorder. Even though it is most difficult to distinguish from various myeloproliferative and myelodysplastic disorders as well as acute myelogenous leukemia, it has rarely been reported to terminate as acute lymphoblastic leukemia (ALL). Only five cases have been reported in the literature; two from the pediatric literature and only three from the adult literature. Of the three adult cases, two were defined by light microscopy alone. Among the cases with follow-up (3/5), all died within 2 weeks to 2 months of diagnosis. We report an additional case in an adult; the ALL was defined by morphology, flow cytometric immunophenotyping, and cytogenetic analysis. The interval from diagnosis of AMF to ALL was 3 months. Our patient was treated with standard therapy for ALL, was in complete remission at last follow-up (3 months off maintenance therapy), and represents the only reported case who attained a complete remission. There are too few cases to determine the prognostic significance of termination of AMF in an acute leukemia of lymphoid origin vs. myeloid origin.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Blast Crisis; Bone Marrow; Chromosome Deletion; Chromosomes, Human, Pair 5; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Cytarabine; Daunorubicin; Disease Progression; Flow Cytometry; Humans; Immunophenotyping; Male; Mercaptopurine; Methotrexate; Neoplastic Stem Cells; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Primary Myelofibrosis; Remission Induction; Vincristine

Currently, no effective treatment is available for the nonlymphoid blast crisis (BC) of chronic myeloid leukemia (CML) and because of this the prognosis for such patients remains invariably poor. In an attempt to determine the results provided by palliative treatment with oral 6-mercaptopurine (6-MP) in the above hematological condition, 30 such patients were analyzed for hospital stay, days of intravenous (i.v.) antibiotics, transfusion requirements, response rate, and survival. Thirty patients with nonlymphoid BC matched for their initial characteristics and treated with different i.v. regimens were used for comparison purposes. Patients managed with 6-MP spent less days in hospital (median: 9, range: 0-46 vs median: 42, range: 5-140; P<0.0001), needed antibiotics for less days (median: 0. range: 0-46 vs median: 20, range: 0-57; P<0.0001), and received less platelet transfusions (median: 0, range: 0-20 vs median: 6, range: 0-63; P=0.004) than those treated with i.v. chemotherapy. Although no complete or partial remission was achieved by patients receiving 6-MP vs six in the i.v. chemotherapy group, no significant difference was observed when the survival of both groups was compared (median: 4.7 months, range: 0.1-22.7 vs median: 3.8 months, range: 0.2-12, respectively). These results indicate that 6-MP therapy constitutes a good palliative treatment for patients with nonlymphoid BC of CML. However, new treatment strategies for this hematological condition are required.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antimetabolites, Antineoplastic; Blast Crisis; Female; Humans; Injections, Intravenous; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mercaptopurine; Middle Aged; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Cyclophosphamide; Cytarabine; Doxorubicin; Eye Neoplasms; Fatal Outcome; Female; Humans; Mercaptopurine; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Vincristine

A 67 year old male developed a therapy related myelodysplastic process culminating in acute myeloid leukemia 16 years following initial treatment for a large cell lymphoma. A second relapse of this leukemia showed 12% blasts including numerous giant blasts. The presence of giant blasts suggested the possibility of relapsed malignant lymphoma, however, flow cytometry and immunohistochemistry identified them as myeloid and chromosomal analysis revealed a near-tetraploid cell line. No evidence of lymphoma was seen. Although remission was induced with chemotherapy he subsequently relapsed with marrow and/or CNS involvement and was maintained on palliative therapy until he developed sepsis and died, 13 months following the observation of tetraploidy and 33 months following the onset of acute leukemia.

Topics: Acute Disease; Aged; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Chromosome Aberrations; Combined Modality Therapy; Cyclophosphamide; Fatal Outcome; Humans; Immunophenotyping; Karyotyping; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma, Large B-Cell, Diffuse; Male; Mercaptopurine; Methotrexate; Neoplasms, Second Primary; Neoplastic Stem Cells; Palliative Care; Polyploidy; Prednisone; Procarbazine; Recurrence; Vincristine

The adenine nucleoside analogue, fludarabine phosphate, in combination with cytosine-arabinoside (Ara-C) and granulocyte-colony stimulating factor (G-CSF) (the so called FLAG regimen) has recently been shown to be effective in the treatment of poor-prognosis acute non-lymphoid leukaemia. We used this combination plus novantrone (FLANG regimen) in a case of Ph1+ chronic myeloid leukaemia (CML) unresponsive to interferon alpha that had progressed to an acute phase, after 3 months of treatment with 6-mercaptopurine and hydroxyurea. The patient was treated with two courses of fludarabine 30 mg/m2 (days 1-5) + Ara-C 2 g/m2 (days 1-5) + novantrone 5 mg/m2 (days 1-3) and G-CSF from day 0 to neutrophil recovery. After the first cycle of chemotherapy, bone marrow blasts decreased from 100% to less than 5% (clinical complete remission), with a progressive clearance of Ph1+ metaphases (from 100% to 12%). At the end of the second course, a progressive increase of blasts was observed again and karyotypic detection of Ph+ cells was also documented (from 12% to 42.9%). During this partial remission, the patient underwent an allogeneic bone marrow transplantation from an HLA matched identical brother. At the time of this report, he is still alive and well and in complete karyotypic remission. This partial therapeutic success was compared with the result obtained in another previously reported CML case: differences in the therapeutic efficacy of protocols employing fludarabine nucleosides and the type of blastic cells involved are discussed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Bone Marrow; Bone Marrow Transplantation; Chromosome Aberrations; Combined Modality Therapy; Cytarabine; Disease Progression; Granulocyte Colony-Stimulating Factor; Humans; Hydroxyurea; Immunologic Factors; Interferon-alpha; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mercaptopurine; Middle Aged; Mitoxantrone; Remission Induction; Vidarabine

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Topics: Adolescent; Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Drug Evaluation; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Male; Mercaptopurine; Middle Aged; Nitrosourea Compounds; Prednisolone; Remission Induction; Vincristine; Vindesine

Topics: Administration, Oral; Aged; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Vitamin A; Vitamin D

Topics: Amsacrine; Blast Crisis; Drug Evaluation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocyte Count; Mercaptopurine; Remission Induction