levoleucovorin and Leukemia--Myeloid

Topics: Adult; Animals; Carboxypeptidases; Carcinoma 256, Walker; Carcinoma, Squamous Cell; Deoxyuridine; Diet; Drug Combinations; Drug Synergism; Folic Acid Antagonists; Humans; Leucovorin; Leukemia L1210; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Mice; Rats; Tritium

The relationship between changes in the bone marrow labeling index and the patient's subsequent response to cycle-specific agents was studied by the South-eastern Cancer Study Group in adults with acute leukemia. Ninety-eight patients were randomized to one of two treatment regimens. Schedule 1 consisted of a single intravenous (i.v.) push of cytosine arabinoside followed in 48 hours by a large dose of oral methotrexate distributed over 24 hours and i.v. vincristine. Leucovorin rescue was employed to control the toxic effects of the high dose methotrexate and the cycle was repeated every 7 days. Schedule 2 differed only in that there were three daily injections of cytosine arabinoside preceding vincristine and methotrexate injections and each cycle was given every 10 days. Cell kinetic studies were performed in 30 patients and revealed that the majority of patients who had a response to therapy had some increase in the marrow labeling index 48 hours after cytosine arabinoside injection. In general, those patients who had no response to therapy had little change. There was no significant difference between schedules in the ability to induce an increase in labeling index 48 hours after cytosine arabinoside or in the increment achieved by the responders. However, there was a significant difference in the response rate seen with these schedules. Schedule 1 achieved only a 24% remission rate in acute nonlymphocytic leukemia (ANLL) while schedule 2 was associated with a 52% remission rate. In acute lymphoblastic leukemia (ALL) both schedules induced a 60% remission rate while none of the four patients with blast crisis of chronic granulocytic leukemia (CGL) responded. Analysis of the characteristics associated with remission revealed that more females achieved a remission than males and that the presence of pretreatment infection was the greatest contributing cause of early death and thus severely limited the ability to achieve a remission. As opposed to the current regimens used in ANLL, schedule 2 did not require significant bone marrow hypoplasia (as judged by the degree of hematological toxicity) to achieve a remission and there was no decrease in response seen with increasing age. The data suggest that increased efficiency of cycle-specific, antitumor agents may occur by increasing the proportion of human leukemic cells in DNA synthesis.

Topics: Adult; Age Factors; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cell Division; Cytarabine; Female; Humans; Leucovorin; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Methotrexate; Middle Aged; Remission, Spontaneous; Sex Factors; Vincristine

Topics: Bone Marrow; Bone Marrow Cells; Cytarabine; Daunorubicin; DNA, Neoplasm; Drug Therapy, Combination; Humans; Kinetics; Leucovorin; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Mitotic Index; Thioguanine

We report our experience of CD34 positive selection as a means of graft T-cell depletion (TCD) in 14 consecutive HLA-identical Peripheral blood stem cells (PBSC) allografts as prophylaxis against graft versus host disease (GVHDp). CD34 positive selection was performed by immunomagnetic separation achieving a median CD34 and T-cell dose of 4.17 (range 1.4-8.50) x 10(6)/kg and 1.89 (range 0.92-13.18) x 10(4)/kg, respectively, in the graft. This represents 4-log depletion of T-cells. The median time to achieve a neutrophil count of 0.5 x 10(9)/l was 15 days and to achieve a platelet count of 50 x 10(9)/l was 20 days. Only four patients developed acute GVHD at a median of 41 days but this was exclusively mild grade I cutaneous disease and settled with oral steroids. Four patients, all of whom had AML, relapsed or progressed after transplant at a median of 161 (range 109-311) days. One of these had been transplanted in early relapse (9% blasts) whilst another was in second remission. The remaining 10 patients are alive and well. The median progression free survival for the whole population is 69% at 686 days. We conclude that CD34 positive selection by immunomagnetic separation in HLA-identical PBSC allografting achieves significant TCD with clinically trivial acute GVHD, prompt engraftment and an acceptable disease relapse risk.

Topics: Acute Disease; Adolescent; Adult; Antigens, CD34; Cyclophosphamide; Cyclosporine; Female; Graft Survival; Graft vs Host Disease; Hematopoietic Stem Cells; Humans; Immunomagnetic Separation; Immunophenotyping; Immunosuppressive Agents; Leucovorin; Leukemia, Myeloid; Lymphocyte Depletion; Male; Methotrexate; Middle Aged; Peripheral Blood Stem Cell Transplantation; T-Lymphocytes, Cytotoxic; Transplantation Conditioning; Transplantation, Homologous; Whole-Body Irradiation

Folinic acid (FA) has been reported to expand the pool of peripheral blood stem cells (PBSC) after chemotherapy. We evaluated the efficacy of FA for harvesting PBSC following cytotoxic chemotherapy in 4 patients with acute leukemia. After achieving a complete remission (CR), 3 courses of chemotherapy for a consolidation of the CR were administered to the patients. Two successive cycles of leukapheresis were performed during the recovery phase from consolidation chemotherapy, which consisted of an intermediate dose of cytosine arabinoside. For the second cycle of leukapheresis, FA was administered intravenously at a dose of 50 mg/day following consolidation. The yields of either mononuclear cells or burst-forming units-erythroid (BFU-E) were not affected by FA administration. In contrast, the yields of colony-forming units-granulocyte/macrophage (CFU-GM) were significantly decreased in all patients compared to the CFU-GM yields after the first cycle of leukapheresis (P = 0.032). Thus FA is considered not to be effective in expanding the peripheral blood progenitor pool when given in a fashion different from the original report.

Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Combined Modality Therapy; Drug Administration Schedule; Female; Hematopoietic Stem Cells; Humans; Leucovorin; Leukapheresis; Leukemia, Myeloid; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Acute Disease; Hematopoietic Stem Cells; Humans; Leucovorin; Leukemia, Myeloid

Topics: Hematopoietic Stem Cells; Humans; Leucovorin; Leukemia, Myeloid

Thirteen adult patients with histologically confirmed lymphoblastic lymphoma were treated with an intensive chemotherapy program consisting of induction with cyclophosphamide, adriamycin, vincristine, and prednisone (modified CHOP); consolidation and central nervous system (CNS) prophylaxis with methotrexate intrathecally and by high-dose intravenous injection, citrovorum factor and L-asparaginase; reinforcement with CHOP; and maintenance with 6-mercaptopurine and methotrexate. Treatment duration was 1 yr. A 14th patient with T-cell acute lymphoblastic leukemia was also treated at presentation by the same regimen. Thirteen patients had at least a mediastinal mass or abnormal cells in the bone marrow; one presented with CNS disease. The median age was 22 yr (range 16--50), and male--female ratio was 2.5:1. All patients had a rapid complete clinical response. Of the 13 patients without initial CNS disease, 4 have relapsed, 3 with primary CNS relapse and 1 with a recurrent abdominal mass. Five patients have died, 2 from drug toxicity, 2 from CNS relapse, and 1 from chronic myelogenous leukemia, which was diagnosed simultaneously with the lymphoblastic lymphoma. The median follow-up is 19 mo, and all patients have completed their planned therapy. At 3 yr, the actuarial survival is 61% and relapse-free survival is 56%.

Topics: Adolescent; Adult; Asparaginase; Central Nervous System Diseases; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Vincristine

The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetrahydrofolate methyltransferase (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13) and normal adult cells are grown in media containing methotrexate and either N5-methyltetrahydrofolate or N5-formyltetrahydrofolate, not only is the selective toxicity of methotrexate demonstrated, but the advantage of using N5-methyltetrahydrofolate in place of N5-formyltetrahydrofolate is also revealed. The implications and applications of this particular combination in the treatment of human cancer are discussed.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Division; Cells, Cultured; Female; Fibroblasts; Humans; Leucovorin; Leukemia L1210; Leukemia, Myeloid; Liver; Methotrexate; Mice; Neoplasms, Experimental; Rats; Tetrahydrofolates

Topics: Breast Neoplasms; Choriocarcinoma; Female; Head; Head and Neck Neoplasms; Humans; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Neoplasm Metastasis; Neoplasms; Ovarian Neoplasms; Pregnancy; Remission, Spontaneous; Uterine Cervical Neoplasms

Topics: Anilides; Child; Child, Preschool; Cyclophosphamide; Female; Humans; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Mercaptopurine; Methotrexate; Prednisone; Urethane; Vincristine

Topics: Adolescent; Child; Hematoma; Hematoma, Epidural, Cranial; Hematoma, Subdural; Humans; Hydrocephalus; Leucovorin; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Meninges; Mercaptopurine; Methotrexate; Pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Radiography; Subarachnoid Hemorrhage; Vinblastine

Topics: Acute Disease; Antimetabolites; Folic Acid; Folic Acid Deficiency; Leucovorin; Leukemia; Leukemia, Myeloid