mercaptopurine and Anemia--Refractory--with-Excess-of-Blasts

Owing to the lack of efficacious treatments for refractory anemia with an excess of blasts (RAEB), evaluation of other therapeutic strategies is necessary, especially in elderly patients. We report herein our experience with an oral triple drug regimen with cyclophosphamide 200 mg/m2 and methotrexate 20 mg/m2 once a week, and 6-mercaptopurine 50 mg/m2 daily for the treatment of RAEB. Eighteen patients with a median age of 62 yr (range 17-80) received a triple drug regimen (TDR), and they were compared with 6 patients who received oxymetholone (2 mg/m2/d) and 9 who received supportive therapy only. Partial response was achieved in 45% of patients receiving TDR. In 77% of patients treated with TDR the number of bone marrow blasts decreased to <5%; however, they persisted with trilineage dyspoietic morphologic changes. Median survival for TDR was 23 months (range 1-96), which was longer than that for the other groups. A slight rise in liver enzymes was the only side effect of TDR. TDR seems to be a useful alternative in patients with RAEB, a finding to be confirmed in further prospective studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anabolic Agents; Anemia, Refractory, with Excess of Blasts; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Oxymetholone; Platelet Count; Survival Analysis; Time Factors

Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT), but membranous glomerulopathy (MG) has rarely been described as a manifestation of chronic GVHD. We report two cases of MG in children who underwent allogeneic HSCT. The clinical findings were characterized by edema of the lower extremities and nephrotic proteinuria in one case and hypertension, hematuria and edema with non-nephrotic proteinuria in the other one. Renal biopsy was consistent with MG and appropriate immunosuppressive therapy was prescribed. Both patients achieved complete remission and are alive without renal disease 4 and 2 years after the diagnosis of MG. The normal levels of albumin and non-nephrotic proteinuria in one of the two cases raise the question of whether the real incidence of MG after HSCT is underestimated. Therefore, we strongly suggest regular urine analysis during the follow-up of children undergoing HSCT in order to diagnose MG early.

Topics: Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Edema; Glomerulonephritis, Membranous; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Male; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Remission Induction; Transplantation Conditioning; Transplantation, Homologous; Vincristine

We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia.

Topics: Aclarubicin; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 20; Combined Modality Therapy; Cytarabine; Disease Progression; Fatal Outcome; Female; Hemorrhage; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemia, Monocytic, Acute; Mercaptopurine; Middle Aged; Neoplasm Proteins; Nuclear Pore Complex Proteins; Prednisolone; Sepsis; Translocation, Genetic

Topics: Anemia, Refractory, with Excess of Blasts; Aneuploidy; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Chromosome Aberrations; Chromosomes, Human, Pair 8; Cladribine; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Fatal Outcome; Female; Gene Amplification; Genes, myc; Humans; Hydrocortisone; Karyotyping; Mercaptopurine; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Vincristine

A 59-year-old man was referred to our hospital because of pancytopenia. Peripheral blood examination showed a WBC of 1,500/microliters with 2% blasts, Hb 8.1 g/dl and a platelet count of 4.1 x 10(4)/microliters. A bone marrow aspiration revealed hyperplasia with proliferation of blasts (15.7%) and myelodysplasia. Chromosome analysis revealed multiple aberrations, including -5, -7, +8. The patient was given a diagnosis of refractory anemia with excess of blasts (RAEB) and treated with combination chemotherapy. Agranulocytosis and high fever remained after chemotherapy, and abdominal pain and diarrhea developed. An abdominal X-ray film and computed tomography scan demonstrated dilated small bowel, thickness of the bowel wall, and ascites. A diagnosis of neutropenic enterocolitis was given. During the WBC recovery period from nadir, massive hematochezia developed in the patient. Angiography detected the leakage of contrast medium from a peripheral region of the first jejunal artery into the jejunal lumen. A partial resection of the jejunum was thus performed, and a histological examination revealed the presence of irregularly dilated blood vessels in the submucosal layer. These findings were consistent with the features of angiodysplasia, and indicate that angiodysplasia should be considered one cause of intestinal hemorrhage in elderly patients during intensive chemotherapy.

Topics: Anemia, Refractory, with Excess of Blasts; Angiodysplasia; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Drug Therapy, Combination; Emergencies; Enterocolitis; Gastrointestinal Hemorrhage; Humans; Idarubicin; Jejunal Diseases; Male; Mercaptopurine; Middle Aged; Neutropenia; Prednisolone; Vincristine

We describe a patient with acute promyelocytic leukemia (APL) who was successfully induced into remission with all-trans retinoic acid (ATRA) and idarubicin, but developed myelodysplastic syndrome (MDS) with monosomy 7 shortly after conclusion of maintenance therapy with idarubicin alternating with 6-mercaptopurine, vincristine, methotrexate and prednisone. Patients on combination regimens of ATRA or other retinoids and chemotherapy, which are being increasingly used in recent years, should be closely monitored for the development of potentially new complications including MDS.

Topics: Adult; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Idarubicin; Karyotyping; Leukemia, Promyelocytic, Acute; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Tretinoin; Vincristine

A 55-year-old female presented with sore throat and slight fever. The patient was admitted to our hospital on December 13, 1993. Full blood count showed hemoglobin 10.7 g/dl, white cell count 960/microliters (neutrophils 14%, lymphocytes 82%, blasts 2%) and platelets 13,000/microliters. Bone marrow examination showed hypocellularity with 4.5% of myeloblast positive for peroxidase. The bone marrow specimens on Dec. 20 showed 15.5% of myeloblasts, some of which had Auer rods. These findings led to the diagnosis of refractory anemia with excess myeloblast in transformation (RAEB-T) of French-American-British Cooperative Group. The patient was transfused and treated with cytarabine ocfosfate (SP-AC) (100 mg tid) and 6-mercaptopurine (50 mg tid) for 14 days. During chemotherapy she complained of nausea and anorexia, but they were managed easily with medication. On Feb. 7, 1994, forty-two days after the start of administration, peripheral blood and bone marrow aspirate were compatible with a complete remission. Although complete remission was sustained with courses of chemotherapy for 4 months, relapse occurred and the patient died of septicemia on August 29, 1994 after induction failure. Observation suggested that oral SPAC in combination with 6-mercaptopurine had a good antileukemic effect on the myelodysplastic syndrome. However, the duration response was short, and further improvement of the therapy is needed.

Topics: Administration, Oral; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleotides; Cytidine Monophosphate; Female; Humans; Mercaptopurine; Middle Aged; Remission Induction

Topics: Aged; Anemia, Refractory, with Excess of Blasts; Drug Evaluation; Humans; Hydroxyurea; Male; Mercaptopurine; Prednisone; Ranitidine

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: Adult; Aged; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Prednisolone; Remission Induction; Vincristine

It has been proposed that intensive chemotherapy ror RAEB is dangerous, and a small dose of ara-C therapy is recommended in many institutes for its ability to differentiate leukemic cells. Combination chemotherapy for RAEB, however, has not been completely evaluated. We introduced B-DOMP therapy, which is used in our hospital, for RAEB. B-DOMP therapy includes Behenoyl ara-C, daunomycin, oncovin, 6-MP and prednisolone, which achieved approximately 80% of complete remission of ANLL for adults. Five males and one female of RAEB, aged 40-74 (median 70), were treated by B-DOMP regimen. Two cases achieved complete remission, 2 remained in partial remission and 2 cases died within one month. In three cases, the cause of death was fungal pneumonia. It must be stressed that life-threatening pneumonia was common after chemo therapy for RAEB, and careful protection against fungal infection using laminarair flow is required.

Topics: Adult; Aged; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Female; Humans; Infusions, Intravenous; Male; Mercaptopurine; Middle Aged; Myelodysplastic Syndromes; Prednisolone; Remission Induction; Vincristine