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[Autologous bone marrow transplantation].

Autologous bone marrow transplantation (ABMT) is a treatment modality increasingly used to treat a growing number of malignancies both in children and in adults. The theoretical rationale is the transfer of dose-action relationship from pharmacological theory to clinical practice. The basic principles, the important indications and the problems of this particular approach are discussed. Normally bone marrow from the iliac crest is used as stem cell source, but the possibilities of the approach become broader by using peripheral blood stem cells (PBSC). This treatment modality and its particular use in neuroblastoma is described demonstrating also the results.

Adult↗

[Acute leukemia: autologous transplantation of bone marrow cells grown in long-term culture containing low molecular weight natural tumour suppressor].

Fourteen patients with acute myelogenous leukemia and 3 patients with acute lymphoblastic leukemia in complete remission underwent autologous transplantation of their bone marrow cells in long-term culture containing low molecular weight-natural tumour suppressor. Their mean age was 27 years (9-35). Preparative regimen included cyclophosphamide and total body irradiation. All patients received no chemotherapy after transplantation. Follow-up for to 45 months showed that 11 patients remained disease-free survival (DFS) at 15 months, 8 at 24 months, 5 at 30 months, and 1 at 43 months. 5 patients relapsed between 6 and 22 months. One case died from sudden death at 6 months. 3.5-year DFS was 62.7 +/- 15.0%.

Adolescent↗

Prognostic factors for autologous bone marrow transplantation in acute leukaemia: a single centre study of 105 patients.

Since the treatment of leukaemia by autologous bone marrow transplantation is becoming increasingly frequent, a retrospective study was undertaken to ascertain factors influencing the evolution of the disease (death and relapse). Data were collected over a period of 11 years for 105 patients with acute leukaemia (60 lymphoid cases and 45 myeloid cases). Multivariate analysis by the Cox model was used to determine prognostic factors for survival and disease free survival (DFS). Overall survival for the entire population was 35% after 8 years while DFS was 33% after 3 years. The major prognostic criteria were granulocyte recovery time (p < 0.001 at 5 weeks) and platelet recovery time (p < 0.02 at 6 weeks). Patients conditioned by an association of polychemotherapy and total body irradiation (TBI) showed a better survival rate than those conditioned by polychemotherapy alone (p < 0.01), with an overall survival of 48% after 3 years for the former group as compared to 19% for the latter. Other parameters influencing survival were the number of graft CFU-GM, sex and age. A knowledge of these factors could provide a means of predicting the long term evolution of leukaemia following autologous bone marrow transplantation. However, the present results require validation by a prospective study taking into account recent therapeutic protocols with haematopoietic growth factors.

Adolescent↗

Autologous stem cell transplantation in chronic myelogenous leukemia: a retrospective analysis of the European Group for Bone Marrow Transplantation. Chronic Leukemia Working Party of the EBMT.

Over a 3 year period (1989-1991), 49 patients who underwent autologous stem cell transplantation (ASCT) for chronic myelogenous leukemia (CML) in chronic phase were reported to the European Bone Marrow Transplant Registry. Most patients had bad prognostic factors. The results were analyzed by 1 September 1993. Hematological recovery was observed in 45 cases and was significantly quicker after blood stem cell transplantation (n = 30) than after BMT (n = 19). Five patients died early and five other patients did not achieve a complete hematological response (CHR) following ASCT. Of the 39 patients who achieved CHR, 34 are still alive 17 to 52 months after ABSCT. Fifteen of the 34 patients who had cytogenetic evaluation exhibited a major response (> or = 65%, Ph-negative metaphases). The actuarial risk of transformation for the 44 evaluable patients was 28.1 +/- 15% (95% CI) and the actuarial survival at three years was 81.5 +/- 15% (95% CI). No factors were found to significantly influence the response rate or the patients' survival. These encouraging results suggest that ASCT by itself could play a role in prolonging survival in CML patients.

Adolescent↗

Autologous bone marrow transplantation in ALL: relapse linked to infusion of tumor cells with the back-up marrow.

A 41-year-old female patient with a pre-B ALL expressing 2 BCR/ABL transcripts e1/a2 and b2/a2 underwent autologous bone marrow transplantation (aBMT) with marrow grown in long-term culture (LTC) for consolidation of remission (CR). After failing to engraft on day 54 she received her back-up marrow. She engrafted by day 23 and developed a full-blown leukemic relapse 2 weeks later. She died from tumor progression 3 months after infusion of the backup marrow. Analysis of the BCR/ABL transcripts weakly positive at time of collection of the backup marrow, negative in the LTC marrow and in the patient after infusion of the LTC marrow, again positive from day 29 after infusion of the backup marrow until death, strongly suggests that infusion of residual tumor cells with the backup marrow contributed to the relapse.

Adult↗

Myeloablative therapy and bone marrow transplantation for Langerhans' cell histiocytosis.

Since the Langerhans Cell (LC) is of haemopoietic origin it may be possible to cure Langerhans cell histiocytosis (LCH) by ablating the patient's own haemopoietic system and replacing it with donor bone marrow--a process termed bone marrow transplantation (BMT). This assumes that the LC itself is the fundamentally abnormal cell though BMT is also a logical therapy even if other cells of haemopoietic origin are eventually shown to be the primary cause of LCH. Marrow ablation/BMT has an appreciable morbidity and mortality and has therefore been reserved for the few LCH patients with a very poor prognosis. The results in these patients engenders cautious optimism that myeloablation/BMT in LCH may have a limited role. Myeloablative chemotherapy or radiotherapy followed by autologous bone marrow 'rescue' is also feasible but risks the return of 'untreated' LCH cells, or their precursors, causing exacerbation of disease.

Adolescent↗

Phase II pilot study of high-dose busulfan and CY followed by autologous BM or peripheral blood stem cell transplantation in patients with advanced chemosensitive breast cancer.

The combination of busulfan and CY ('BU-CY') has been widely employed as a conditioning regimen for patients undergoing BMT for hematologic malignancies. However, little information is available regarding the utility of BU-CY in treating patients with advanced breast cancer. Fifteen patients with heavily pretreated Stage IIIB or Stage IV chemosensitive breast cancer were treated with busulfan (16 mg/kg) and CY (6000 mg/m2) followed by rescue with autologous BM or autologous peripheral blood stem cells. Toxicity and engraftment parameters were similar to those observed in patients receiving BU-CY for other indications. The overall response rate was 87%, with 53% of patients achieving CR. The median progression-free survival was 164 days, and the median overall survival was 292 days. We conclude that BU-CY is able to induce remissions in a high percentage of patients with heavily pretreated advanced breast cancer. However, remissions are brief, and alternative strategies for patient selection and/or management will be necessary to improve on these results.

Adenocarcinoma↗

New developments in stem cell detection and stem cell selection in the context of autologous transplantations.

The concept of bone marrow transplantation is now enlarged to hemopoietic stem cell transplantation. Basic research on hemopoiesis, its regulation and markers, allowed concrete progress in the field of autologous transplantation. We report two applications: 1) the improvement of methods for detection of stem cells, which ensure engraftment, using recombinant growth factors, allowed a more sensitive determination of chemotherapeutic in vitro treatments toxicity upon normal progenitor cells; 2) large scale selection of hemopoietic progenitor/stem cell using the CD 34 immunological marker: its application to autologous transplantation.

Bone Marrow Purging↗

Autotransplantation in multiple myeloma.

High-dose chemotherapy with autologous hematopoietic stem cell reconstitution is efficacious in the treatment of multiple myeloma. The various preparative regimens, sources of hematopoietic stem cells, and post-transplant immunomodulation are discussed. Tandem autotransplantation following intravenous melphalan chemotherapy has low morbidity and mortality even in patients with refractory disease. The most encouraging results are observed in patients undergoing high-dose chemotherapy with less prior treatment, lower tumor mass, and sensitive disease.

Adjuvants, Immunologic↗

Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow.

Polymerase chain reaction (PCR) amplification of the t(14;18) has been shown to be a highly sensitive method to detect minimal residual disease in patients with non-Hodgkin's lymphoma (NHL) whose tumors bear this translocation. The ideal tissue source to detect residual lymphoma would be from a previously involved lymph node. However, lymphoid tissue is rarely available once patients achieve complete remission. Although PCR amplification has been used to detect residual lymphoma cells in both bone marrow (BM) and peripheral blood (PB) of patients in complete remission, it is presently unknown whether BM and PB are equivalent tissue sources to detect residual disease. In the present study, we compared the clinical utility of the detection of residual lymphoma in both the BM and the PB of patients with advanced-stage non-Hodgkin's lymphoma before, at the time of, and after high-dose therapy and autologous BM transplantation (ABMT). The detection of residual lymphoma in either the BM or PB was associated with decreased disease-free survival. However, in the present study, 44% of patients who relapsed had no evidence of circulating lymphoma cells in their PB. At the time of BM harvest, PCR-detectable residual lymphoma cells were detected in 211 of 212 patients; although, in a subset of these patients analyzed, lymphoma cells were detected in the peripheral blood of only 49% of patients. When residual lymphoma cells within the autologous BM are infused into the patient these cells are rapidly detectable circulating in the PB in the patient. These cells continue to circulate during the immediate posttransplant period and be detectable in the PB in the majority of patients who are infused with marrow containing residual lymphoma. We conclude that BM is a more informative tissue source than PB in detecting minimal residual disease at the time of and after ABMT, and that contamination of PB early after ABMT appears to be the consequence of reinfusion of lymphoma cells within autologous marrow.

Base Sequence↗