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PubMed1994

Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow.

We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.

Adolescent↗
PubMed1990

[Treatment results of bone marrow transplantation in Kyushu Cancer Center. Bone Marrow Transplantation Team].

Twenty children with various hematological malignancies (nine with acute lymphoblastic leukemia, eight with acute non-lymphoblastic leukemia, two with chronic myelogenous leukemia, one with malignant lymphoma and one with 7-monosomy) and four with severe aplastic anemia were treated with allogeneic or syngeneic bone marrow transplantation (BMT) between September 1977 and September 1988. Eleven patients are surviving currently and ten are disease free 8 to 51 months after BMT. Conditioning regimen consisted of total body irradiation (TBI) and cyclophosphamide in twenty patients. Two patients did not receive TBI. Graft failure was observed in five patients and complete recovery of recipient marrow was seen in two of them. Eleven patients developed acute graft-versus-host disease (GvHD) with grade I-II in eight patients. Three patients suffered from chronic GvHD. Seven patients with acute leukemia relapsed and all but one died of leukemia. Early death occurred in two undergone BMT in poor clinical conditions. Performance status in 100% in surviving patients except one. Efforts to improve these results are that BMT should be considered early in the course of their disease for patients who are at risk for relapse with conventional chemotherapy and improved conditioning regimens to reduce leukemia relapse after BMT for patient with the second or subsequent remission.

Adolescent↗
PubMed1999

Comparative testing of peripheral blood and bone marrow for BCR-ABL transcripts in patients post allogeneic bone marrow transplantation and during interferon treatment for chronic myeloid leukemia.

Patients with CML post allogeneic BMT or during treatment with Interferon were monitored in bone marrow and peripheral blood for BCR-ABL transcripts by RT-PCR and in the majority of cases also by Southern blotting. Bone marrow and peripheral blood samples were obtained simultaneously and tested by RT-PCR with the objective to determine the usefulness to follow CML patients by testing peripheral blood rather than bone marrow samples. For the purpose of this study we have considered the test results obtained from bone marrow samples as the standard. A total of 111 CML patients were examined who underwent either an allogeneic BMT (n=91) or were treated with Interferon (n=20) amounting to a total of 163 assessments for BCR-ABL. Concordance of results was observed in 153 samples (93.9%). 10 samples showed discordance. Seven of these were subjected to repeat testing by RT-PCR. The previously obtained discordant results were confirmed. The sensitivity of peripheral blood assays was calculated to be 96.2% with a specificity of 89.5%. RT-PCR results restricted to Southern blot negative patients showed concordance of bone marrow and peripheral blood in 91.1% of tested samples with a sensitivity of 92.7% and a specificity of 88.6%. The subset of patients in which Southern blot testing was not available showed concordance at a similar level. Complete concordance was seen in all patients that were found to be positive by Southern blotting. We conclude from this study that peripheral blood testing for BCR-ABL transcripts by RT-PCR is a test with high sensitivity and specificity and may potentially replace bone marrow testing. This approach will probably result in a high level of acceptance by patients and may permit more frequent monitoring.

Blotting, Southern↗
PubMed1975

Autologous bone marrow transplantation.

Bone marrow cells can be aspirated from patients with malignant disorders, stored at low temperatures, and reinfused into the same patient at a later date. In the past, the results of this autologous bone marrow transplantation were equivocal. With the availability of better methods for cryopreservation and more accurate assays for the survival of hemopoietic progenitor cells, there has been a resurgence of interest in this procedure.

Animals↗
PubMed2002

Unrelated bone marrow transplantation in thalassemia. The experience of the Italian Bone Marrow Transplant Group (GITMO).

BACKGROUND AND OBJECTIVES: Allogeneic bone marrow transplantation (BMT) is a widely accepted therapeutic approach in homozygous beta-thalassemia. However, the majority of patients do not have a genotypically identical donor within the family. This prompted us to conduct a pilot study to investigate the feasibility of matched unrelated bone marrow transplantation in thalassemia. The major drawback was the high risk of immunologic and transplant-related complications, mainly graft-versus-host disease (GvHD) and graft failure. DESIGN AND METHODS: Our aim was to reduce this risk through careful selection of donor/recipient pairs. HLA haplotypes that show a high linkage disequilibrium among their class I, class II and class III alleles are considered extended or ancestral haplotypes. RESULTS: These haplotypes are conserved and can be shared by apparently unrelated individuals. Our study shows that matching for these haplotypes significantly improves the outcome of unrelated bone marrow transplantation in thalassemia. In fact, results were comparable to those obtained in transplants using HLA-identifical family donors. INTERPRETATION AND CONCLUSIONS: Better results were obtained in patients with lesser iron overload and when the donor shared an identity for the DPB1 alleles.

Adolescent↗
PubMed2002

Nutritional and metabolic support in patients undergoing bone marrow transplantation.

Bone marrow transplantation (BMT) is a sophisticated procedure consisting of the administration of high-dose chemoradiotherapy followed by intravenous infusion of hemopoietic stem cells to reestablish marrow function when bone marrow is damaged or defective. BMT is used in the treatment of solid tumors, hematologic diseases, and autoimmune disorders. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing BMT to minimize the nutritional consequences of both the conditioning regimens (eg, mucositis of the gastrointestinal tract) and complications resulting from the procedure (eg, graft versus host disease and venoocclusive disease of the liver). Although artificial nutrition is now recognized as the standard of care for BMT patients, defined guidelines for the use of artificial nutrition in this clinical setting are lacking. During the past 2 decades, artificial nutrition in BMT patients has moved from simple supportive care to adjunctive therapy because of the possible benefits, not strictly nutritional, of specialized nutritional intervention. Although data exist documenting the beneficial role of special nutrients, such as lipids and glutamine, in the management of BMT recipients, the results obtained to date are controversial. The reasons for this controversy may reside in the heterogeneity of the patients studied and of the study designs. This review focuses on the need to correctly identify the different patterns of BMT to achieve reproducible and reliable data, which may in turn be used to devise precise guidelines for the use of specialized artificial nutrition in BMT patients.

Adult↗
PubMed1992

In vitro purging of clonogenic leukemic cells from human bone marrow by heat: simulation experiments for autologous bone marrow transplantation.

In order to apply a simple purging method by heat to autologous bone marrow transplantation (ABMT), we have revaluated the ability to purge clonogenic leukemic cells from the simulated marrow mixture of normal marrow cells and leukemic cell lines (HL-60, Molt-3 and HEL) in vitro by heat, using two different clonogenic assays for normal granulocyte-macrophage progenitors (CFU-GM) and leukemic cell lines. It appeared that in vitro hyperthermia (42 degrees C for 120 min) is able to selectively remove clonogenic leukemic cells from simulated tumor cell-normal marrow mixtures even when leukemic cell concentrations are increased up to 3 x 10(6) cells/ml in vitro, and results in a 4-6 log destruction of clonogenic leukemic cells/ml according to a limiting dilution assay, while leaving half of normal CFU-GM surviving. The hyperthermic purging of clonogenic leukemic cells was not affected in the presence of normal marrow cells in vitro. This high level of clonogenic leukemic cell depletion by heat correlated with that of immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous marrow grafts before ABMT.

Bone Marrow Purging↗