Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between August 1990 and August 1995, 231 patients (median age 51, 53% Durie-Salmon stage III, median serum beta-2-microglobulin 3.1 g/L, median C-reactive protein 4 g/L) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy ("Total Therapy"). Remission induction utilized non-cross-resistant regimens (vincristine-doxorubicin-dexamethasone [VAD], high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection, and etoposide-dexamethasone-cytarabine-cisplatin). The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete (CR) or partial (PR) remission was maintained after the first transplant; in case of less than PR, total body irradiation or cyclophosphamide was added. Interferon--2b maintenance was used after the second autotransplant. Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle. Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84% and 71% (the majority within 8 and 15 months, respectively). Eight patients (3%) died of toxicity during induction, and 2 (1%) and 6 (4%) during the two transplants. True CR and at least a PR (PR plus CR) were obtained in 5% (34%) after VAD, 15% (65%) at the end of induction, and 26% (75%) after the first and 41% (83%) after the second transplants (intent-to-treat). Median overall (OS) and event-free (EFS) survival durations were 68 and 43 months, respectively. Actuarial 5-year OS and EFS rates were 58% and 42%, respectively. The median time to disease progression or relapse was 52 months. Among the 94 patients achieving CR, the median CR duration was 50 months. On multivariate analysis, superior EFS and OS were observed in the absence of unfavorable karyotypes (11q breakpoint abnormalities, -13 or 13-q) and with low beta-2-microglobulin at diagnosis. CR duration was significantly longer with early onset of CR and favorable karyotypes. Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly, independent of cytogenetics and beta-2-microglobulin. Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients, using multi-regimen induction and tandem transplantation followed by interferon maintenance. As a result, the proportion of patients attaining CR increased progressively with continuing therapy. This observation is particularly important because CR is a sine qua non for long-term disease control and, eventually, cure.
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PMID:Total therapy with tandem transplants for newly diagnosed multiple myeloma. 986 46

High-dose chemotherapy followed by autologous stem cell transplant (ASCT) leads to durable remissions in approximately half of patients with chemosensitive relapsed or refractory aggressive lymphomas; however, many will relapse despite ASCT secondary to persistent minimal residual disease (MRD) or malignant graft contamination. Post-transplant rituximab may eradicate MRD. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) might enhance the efficacy of rituximab by augmenting antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that given together, rituximab, GM-CSF, and IL-2 might eradicate MRD and improve event-free survival following ASCT. Forty-six patients with relapsed non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were enrolled. Stem cells were mobilized with G-CSF and GM-CSF following chemotherapy. Following BEAM conditioning, patients received GM-CSF until neutrophil engraftment. Between days + 30 and + 120, patients received one dose of rituximab 375 mg/m(2) (cycle 1), followed by three cycles of GM-CSF 250 microg/m(2)/day SQ days 1-5, IL-2 1.5 x 10(6) IU/m(2)/day SQ days 6-12, and rituximab 375 mg/m(2) IV day 9, repeated every 21 days. Thirty-eight patients were eligible for post-ASCT immunotherapy. Nine patients completed 1-2 cycles and 21 completed 3-4 cycles; eight patients did not receive post-ASCT immunotherapy. Grade 3-4 neutropenia and grade 3 thrombocytopenia were observed. With a median follow-up of 30 months, the estimated 5-year OS and EFS for all patients eligible for immunotherapy are 65% and 45%, respectively. Post-ASCT immunomodulation with rituximab, IL-2, and GM-CSF was feasible and safe, but not all patients were able to continue on to post-ASCT immunotherapy.
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PMID:Phase II study of immunomodulation with granulocyte-macrophage colony-stimulating factor, interleukin-2, and rituximab following autologous stem cell transplant in patients with relapsed or refractory lymphomas. 2049 94