Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation.
(73/1945)
Therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML) after high-dose chemotherapy (HD-CT) and autologous stem cell transplantation (ASCT) for malignant diseases have become an important problem. The actuarial risk has varied, but has often been high if compared to the risk after conventional therapy. Prior chemotherapy with large cumulative doses of alkylating agents is the most important risk factor. In addition, patient age and previous radiotherapy, particularly the use of total body irradiation (TBI) in the preparative regimen for ASCT, have been identified as risk factors. In 3 studies, patients transplanted with CD34(+ )cells from peripheral blood after chemotherapy priming showed a higher risk of t-MDS or t-AML than patients transplanted with cells isolated from the bone marrow without priming. To what extent this higher risk relates to the prior therapy with a different contamination with preleukemic, hematopoietic precursors of the CD34(+) cells obtained by the 2 methods, or is a direct result of chemotherapy priming, or of an increasing awareness of these complications, remains to be determined. The latent period from ASCT to t-MDS and t-AML has often been short, 12 months or less in 27% of the patients. Bone marrow pathology of early cases of t-MDS after ASCT has often been neither diagnostic nor prognostic, but most patients presented chromosome aberrations, primarily deletions or loss of the long arms of chromosomes 5 and 7. The prognosis was in general poor, although 17% with indolent t-MDS survived more than 18 months from diagnosis, and most of these presented a normal karyotype or a single chromosome aberration. (+info)
Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation.
(74/1945)
We examined the feasibility of a community blood bank granulocyte transfusion program utilizing community donors stimulated with a single-dose regimen of subcutaneous granulocyte colony-stimulating factor (G-CSF) plus oral dexamethasone. The recipients of these transfusions were neutropenic stem cell transplantation patients with severe bacterial or fungal infection. Nineteen patients received 165 transfusions (mean 8.6 transfusions/patient, range 1-25). Community donors provided 94% of the transfusions; relatives accounted for only 6% of the transfusions. Sixty percent of the community donors initially contacted agreed to participate, and 98% of these individuals indicated willingness to participate again. Transfusion of 81.9 +/- 2.3 x 10(9) neutrophils (mean +/- SD) resulted in a mean 1-hour posttransfusion neutrophil increment of 2. 6 +/- 2.6 x 10(3)/microL and restored the peripheral neutrophil count to the normal range in 17 of the 19 patients. The buccal neutrophil response, a measure of the capacity of neutrophils to migrate to tissue sites in vivo, was restored to normal in most patients following the transfusion. Chills, fever, and arterial oxygen desaturation of >/= 3% occurred in 7% of the transfusions, but these changes were not sufficient to limit therapy. Infection resolved in 8 of 11 patients with invasive bacterial infections or candidemia. These studies indicate that transfusion of neutrophils from donors stimulated with G-CSF plus dexamethasone can restore a severely neutropenic patient's blood neutrophil supply and neutrophil inflammation response. Further studies are needed to evaluate the clinical efficacy of this therapy. (+info)
Filgrastim as an alternative to donor leukocyte infusion for relapse after allogeneic stem-cell transplantation.
(75/1945)
PURPOSE: Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT. PATIENTS AND METHODS: Fourteen patients with hematologic malignancies were treated with filgrastim at relapse after alloSCT. Filgrastim was given at 5 mcg/kg/d subcutaneously for 21 consecutive days. Response was evaluated at 7 days after completion of filgrastim. Immunosuppressants, if present, were rapidly tapered to complete discontinuation at the time of relapse. RESULTS: Three patients were not assessable for response because additional therapy was necessary before completion of filgrastim. Six patients (43%) achieved a complete response on an intent-to-treat basis. When response was evaluated based on relapse type, three of four cytogenetic relapses, two of three morphologic relapses, and one of four hematologic relapses achieved a complete remission. Two responses were observed in patients who were completely off of any immunosuppression at the time of relapse. Six patients developed chronic graft-versus-host disease. The event-free and overall survival rates for all 14 patients are 43% and 73%, respectively. CONCLUSION: The use of filgrastim with rapid discontinuation of immunosuppression results in response rates that are similar to results using DLI. Filgrastim could be considered as an alternative or an adjunct to DLI for relapses after alloSCT. (+info)
Fusion of the nucleoporin gene, NUP98, and the putative RNA helicase gene, DDX10, by inversion 11 (p15q22) chromosome translocation in a patient with etoposide-related myelodysplastic syndrome.
(76/1945)
We report a 50-year-old man who developed therapy-related myelodysplastic syndrome after treatment with etoposide-including chemotherapy for extratesticular germ cell tumor. Chromosomal analysis showed inversion 11 (p15q22) translocation. Reverse transcriptase-polymerase chain reaction amplification of patient RNA showed a fusion transcript of nucleoporin gene NUP98, and putative DEAD-box RNA helicase gene DDX10. NUP98 is implicated in the transformation through aberrant nucleocytoplasmic transport. DDX10 is suggested to be involved in ribosome assembly. The NUP98-DDX10 fusion transcript may promote the development of secondary hematological malignancies caused by DNA-topoisomerase II inhibitors through aberrant nucleocytoplasmic transport and/or alteration in ribosome assembly. (+info)
A randomised study of allogeneic transplantation with stem cells from blood or bone marrow.
(77/1945)
Sixty-one consecutive adult patients with leukaemia, primary myelofibrosis or myelodysplastic syndrome with an HLA-identical or one antigen mismatched family donor were randomised to allogeneic transplantation with PBPC or BM. Progenitor cells were mobilised into the blood by giving the donors 10 microg/kg/day G-CSF subcutaneously for 5-7 days. G-CSF was not given to patients after transplantation. The time to neutrophil counts >0.5 x 109/l was 17 days (95% CI 15.2-18.8 days) in the PBPC group compared to 23 (95% CI 20.3-25.7 days) in the BM group (P = 0.0005). The time to platelet counts >20 x 109/l was 13 days (95% CI 11.7-14.3 days) in the PBPC group and 21 days (95% CI 18.7-23.3 days) in the BM group (P = 0.0005). Acute GVHD of grades II-IV developed in six patients transplanted with PBPC and three patients transplanted with BM. The numbers of patients with chronic GVHD were 15 and 8, respectively. Transplant-related mortality and leukaemia-free survival showed no significant differences. Transplantation with PBPC appears preferable for the recipient due to faster neutrophil and platelet recovery. However, the final conclusion can not be drawn before long-term results on chronic GVHD and relapse incidence in longer randomised trials are available. (+info)
Validation of self-reported complications by bone marrow transplantation survivors.
(78/1945)
Self-administered questionnaires are commonly used to measure exposures and outcomes in epidemiological research and thus need good validity. With increasing numbers of cancer survivors, there is interest in the ongoing assessment of therapy-related complications. A medical record validation of patient-reported complications following bone marrow transplantation (BMT) was performed using a self-administered questionnaire. The study population consisted of 100 patients who had undergone BMT at the City of Hope. The following self-reported complications were validated using medical records: ocular, endocrine, cardiovascular, musculoskeletal, pulmonary, gastrointestinal, neurological, graft-versus-host disease, and subsequent cancers. Using information from medical records as the standard, sensitivities ranged from 52.9% for subsequent cancers to 100% for avascular necrosis and hypothyroidism. Specificities ranged from 75.4% for ocular complications to 100% for avascular necrosis. There was intermediate to excellent agreement (kappa = 0. 4-1.0) for all complications evaluated. Thus, the agreement between self-reporting and medical records was good for complications with clear diagnostic criteria that are easily communicated to the patient, but was diminished for complications with non-established diagnostic criteria (xerophthalmia) or a fluctuating course (peripheral neuropathies and hypertension). Overall these results suggest that cancer survivors can self-report serious complications with an acceptable level of accuracy in epidemiological research. (+info)
Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome.
(79/1945)
We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT. With a median follow-up of 36 months after ASCT, there were no cases of MDS/AML among the 229 patients. In the selected cohort of 60 patients, three (5%) showed clonal chromosomal abnormalities (two single trisomy X and one t(1;6)), whereas two additional patients showed non-clonal reciprocal translocations. Two of the patients with clonal aberrations had blood cytopenias as well as subtle dysplastic pictures in BM which were not classifiable as MDS according to the FAB criteria. Similar dysplastic features were also observed in four patients with normal karyotypes. All cytogenetic aberrations were transient and disappeared, except a +X detected by FISH in a residual cell population in one of the patients. Retrospective cytogenetic and FISH studies of samples obtained after six cycles of FAC/FEC and before transplant demonstrated no chromosomal abnormalities in any of the five patients with post-ASCT karyotypic changes. Early changes in karyotype detected in breast cancer patients following ASCT are transient and do not correlate with or predict development of MDS/AML. As these aberrations were not present before ASCT, they may be related to the HDCT regimen or transplant procedure rather than to the prior adjuvant therapy. Our results suggest that ASCT may be less likely to cause MDS or AML in breast cancer patients as compared to other malignancies. Bone Marrow Transplantation (2000) 25, 1203-1208. (+info)
Allelic loss in the progression of myelodysplastic syndrome.
(80/1945)
To elucidate the genetic events that may play an important role in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML), we performed allelotype analysis of 24 individuals using matched MDS and AML samples from the same patients. Because the evolution can take years to occur, we used DNAs extracted from archival samples. These samples were analyzed with 79 microsatellite markers, which mapped to each of the autosomal arms except the short arms of the acrocentric chromosomes. Loss of heterozygosity on at least one locus was observed in 18 of the 24 cases (75%) as the disease progressed. Frequent allelic loss in >20% of the informative cases was observed on chromosome arms 6q (31%), 7p (23%), 10p (31%), 11q (27%), 14q (25%), and 20q (23%). Although cytogenetic information was available for many of our cases with allelic loss on 6q, 7p, 10p, 11q, 14q, and 20q, no deletions were observed on these arms. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost per total number of arms with information, showed a median value of 0.06 and a mean of 0.15 (range, 0-0.59). No microsatellite instability at more than one marker was found in any of the samples. These results suggest that tumor suppressor genes exist on 6q, 7p, 10p, 11q, 14q, and 20q that have an important role in the evolution of MDS to AML when they are mutated. (+info)