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Biomedical subjects

R Champlin

Publications and source records attributed to R Champlin.

At least 181 records · Page 10Linked to original sources
PubMed1993

Effect of induction cytarabine dose intensity on long-term survival in acute myelogenous leukemia: results of a randomized, controlled study.

The optimal dose and schedule of cytarabine in induction chemotherapy of newly diagnosed acute myelogenous leukemia is not established. We compared the use of cytarabine 200 mg/m2/day by continuous infusion for seven days to an intermediate-dose of cytarabine, 500 mg/m2 every 12 hours for 12 doses. Thirty-seven of 52 patients assigned to conventional-dose cytarabine achieved complete remission (71%) and the actuarial disease-free and overall survival after achieving remission were 22 +/- 16% and 31 +/- 19% respectively. Thirty-seven of 50 patients assigned to intermediate-dose cytarabine achieved remission (74%) and the actuarial disease-free and overall survival after achieving remission were 26 +/- 16% and 39 +/- 18% respectively. There were no statistically significant differences in complete remission rate, actuarial leukemia-free survival or overall survival between the groups. The most significant predictor for survival was age. Actuarial two year leukemia-free survival and overall survival for patients age > 60 were 8 +/- 15% and 20 +/- 19% respectively compared to 36 +/- 14% and 54 +/- 15% for patients age < or = 60 (P = .058 and .01, respectively). Induction regimen did not significantly affect disease free or overall survival for patients under or over age 60. We conclude that intermediate-dose cytarabine did not substantially improve results of induction for newly diagnosed acute myeloid leukemia.

Adolescent↗
PubMed1993

Use of cytosine arabinoside and total body irradiation as conditioning for allogeneic marrow transplantation in patients with acute lymphoblastic leukemia: a multicenter survey.

We report the experience of 14 centers which have used the combination of cytosine arabinoside (ara-C; 24-36 g/m2) and total body irradiation (TBI) to prepare 213 patients with acute lymphoblastic leukemia (ALL) for allogeneic BMT. The overall 3-year disease-free survival (DFS) probability is 38% (95% CI: 31-45%); 75 patients died of complications and 51 relapsed. Multivariate analysis identified three factors independently associated with outcome: age, remission/relapse status and patient-donor relationship. The 3-year DFS probability is 52% (41-63%) for the 106 patients aged 0-11 and 25% (16-33%) for the 104 aged 11+ years; the DFS probability was 54% (34-74%), 41% (32-49%) and 19% (5-33%) for those in first remission, later remissions and relapse respectively. Older patients suffered both more toxic deaths and more relapses than young ones. No other covariate was found to predict for outcome. The results using ara-C-TBI are similar to those achieved using cyclophosphamide plus TBI to prepare ALL patients for BMT, perhaps because a seemingly lower relapse rate is offset by more toxic deaths particularly in older patients. Therapeutic trials should focus on reducing toxicity while maximizing antileukemic efficacy, and should stratify for patient and disease-related factors.

Adolescent↗
PubMed1992

Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia.

Modern induction chemotherapy produces 60% to 80% complete remissions in adults with newly diagnosed acute myelogenous leukemia. A major challenge is to eradicate subclinical disease in remission and prevent leukemic relapse. We analyzed the long-term results of high-dose cytarabine-anthracycline consolidation chemotherapy without maintenance treatment and examined the effect of major prognostic factors, including age, sex, history of preleukemia, and cytogenetics. Two hundred twenty-seven patients with newly diagnosed acute leukemia were enrolled on two sequential studies conducted from 1982 to 1991. One hundred fifty-one patients (67%) achieved a complete remission. One hundred twenty-three patients were eligible for high-dose cytarabine-based consolidation administered in two to three courses. After a median follow-up of 4.8 years, 40 patients remain alive, with 28 in continued remission. Median remission duration for all eligible patients is 12.8 months, and actuarial leukemia-free survival (LFS) at 5 years is 26% +/- 8%. Advanced age and male sex were negative prognostic indicators for LFS. For patients < or = 45 years of age, 5-year LFS was 35% +/- 13%, as compared with 18% +/- 11% for patients greater than age 45 (P = .03). Toxicity of consolidation chemotherapy included treatment-related death in nine patients and serious neurotoxicity in five. Our results show an improved LFS for younger patients treated with high-dose cytarabine-based consolidation. There was no apparent benefit for older patients compared with reported data with less intensive regimens.

Adult↗
PubMed1992

Detection of minimal residual disease by polymerase chain reaction of bcr/abl transcripts in chronic myelogenous leukaemia following allogeneic bone marrow transplantation.

The prognostic significance of detecting minimal residual disease by polymerase chain reaction (PCR) amplification of bcr/abl mRNA transcripts was investigated in 27 bone marrow samples from 20 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukaemia (CML) in complete cytogenetic remission following allogeneic bone marrow transplantation. Sixteen were transplanted in first chronic phase, two were in second chronic phase, one was in accelerated phase and one was in blast crisis. All 20 achieved complete cytogenetic remission post transplant and 15 patients had detectable bcr/abl mRNA by PCR from 2 to 22 months following the procedure. One of these patients had graft failure and one died from graft-versus-host-disease at 7 months. Of the remaining 13 PCR-positive patients, only one (8%) relapsed after 23 months; the other 12 were alive and still in remission after a median follow-up of 16+ months (ranging 5+ to 29+ months). Five patients were PCR negative; all are alive in complete clinical and cytogenetic remission at 10+, 11+, 19+, 25+ and 25+ months post transplant. In this study, detection of subclinical Ph1-positive cells by PCR was not associated with imminent clinical or cytogenetic relapse. Since late recurrence may potentially occur, long-term follow-up is required to definitely determine the prognostic value of the PCR assay.

Adult↗
PubMed1992

A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia.

The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100-200 mg/m2/d, although higher doses have been proposed to increase the concentration of the active metabolite ara-CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional-dose cytarabine (200 mg/m2/d by continuous infusion) or an intermediate-dose of cytarabine (500 mg/m2 every 12 h). 36/51 (71%) patients assigned to conventional-dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate-dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age greater than 60 assigned to conventional-dose cytarabine and 10/17 assigned to intermediate-dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P = 0.004). Actuarial 4-year disease-free survival for patients assigned to conventional-dose cytarabine was 20 +/- 16% versus 28 +/- 17% for patients assigned to intermediate-dose cytarabine (P = 0.9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.

Adolescent↗
PubMed1991

In vitro production of granulocyte-macrophage colony-stimulating factor in aplastic anemia: possible mechanisms of action of antithymocyte globulin.

Various abnormalities of lymphokine production have been described in patients with aplastic anemia. To determine if abnormal production of hematopoietic growth factors could contribute to the process of aplastic anemia we studied the in vitro production of human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) by phytohemagglutinin (PHA)- and antithymocyte globulin (ATG)-stimulated peripheral blood lymphocytes from 29 patients with aplastic anemia and 15 normal controls. GM-CSF production in response to 1% PHA was seen in nearly all samples (43 of 44) and similar amounts of GM-CSF were produced by patients with aplastic anemia and normal controls. Production of GM-CSF by ATG-stimulated lymphocytes was seen in 7 of 23 patients with aplastic anemia (30%); two of these patients also demonstrated low-level spontaneous production of GM-CSF. Production of GM-CSF in response to ATG was also seen in 2 of 11 normal controls (18%) and barely detectable spontaneous production of GM-CSF was seen in both. Biologically active IL-3 could also be detected in PHA- or ATG-stimulated peripheral blood mononuclear cells in several patients and normal controls. Our results indicate that lymphocytes from patients with aplastic anemia can be stimulated in vitro to produce normal quantities of GM-CSF, suggesting that impaired potential for production of T-cell derived hematopoietic growth factors is unlikely to account for the marrow hypoplasia seen. In several patients overproduction of GM-CSF was observed, consistent with the notion that some patients with aplastic anemia may have circulating activated T cells. We also demonstrate that ATG can stimulate the production of growth factors such as IL-3 and GM-CSF, supporting the role for ATG in stimulating hematopoiesis.

Adult↗
PubMed1991

Immunobiology of bone marrow transplantation as treatment for hematologic malignancies.

In conclusion, graft-versus-leukemia is important to prevent leukemia relapse following allogeneic bone marrow transplantation. This beneficial GVL effect is at least partly mediated by T-lymphocytes and is greatest in transplants from HLA-nongenotypically identical donors. GVL is associated with the presence of GVHD, although preliminary studies suggest it may be possible to separate these two processes. Improvement in treatment results requires innovative effective therapies to enhance the direct antineoplastic effects of the preparative regimen or immune-mediated antileukemia mechanisms.

Bone Marrow Transplantation↗
PubMed1990

Are some cases of acute leukemia with t(8;21) hybrid leukemias?

Translocations between chromosomes 8 and 21, t(8;21)(q22;q22), occur most commonly in acute myelogenous leukemia (AML) of the M2 FAB type. We studied two cases of acute leukemia with t(8;21) by immune phenotyping and IgH and T-cell receptor beta chain gene rearrangement analyses. These cases had increased blasts in bone marrow (greater than 50%). Auer rods, and evidence of granulocyte maturation. Blasts from both cases expressed CD19(B4), a B-cell antigen, as well as myeloid antigens including CD13(My7) and CD33(My9). HLA-DR, CD34, and TdT were also strongly positive. IgH or TCR beta gene rearrangements were not detected. We suggest that some cases of acute leukemia with t(8;21) may be hybrid leukemias with transformation in a multipotent stem cell.

Adult↗