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PubMed1993

Bone marrow transplantation in sickle cell disease: the Belgian experience.

Twenty eight patients underwent bone marrow transplantation (BMT) for sickle cell anemia in Belgium. The patients were originating from Central Africa, were young and symptomatic. Engraftment occurred in all patients and was sustained in 25. In 3 patients, a bone marrow rejection was observed. One of these patients underwent a second BMT and had an uneventful recovery. One patient died 3 months after BMT of graft-versus-host disease (GVHD). Twenty seven patients are alive and 25 are free of vaso-occlusive related manifestations with a follow-up ranging from 4 to 78 months. So far, eight patients went back to Africa and continue to do well.

Adolescent↗
PubMed1993

Bone marrow transplantation (BMT) in 14 children with severe sickle cell disease (SCD): the French experience. GEGMO.

Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), osteitis (n:3), osteonecrosis (n:3), strokes (n:3) or frequent massive deglobulisation (n:2). Two children undergone splenectomy, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), North-Africa (n:3) or West Indies (n:1). At BMT, they were 2y 3m to 14y 9m old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), > 16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Unexpected complications after bone marrow transplantation in transfusion-dependent children.

Ten patients on transfusion-chelation programs were treated with bone marrow transplantation (BMT). The busulfan-cyclophosphamide conditioning regimen was inadequate in the 6 beta thalassemia major patients, resulting in marrow rejection problems for 3. Post BMT one patient remains with thalassemia major and two have mixed chimerism with a clinical status of thalassemia intermedia. Three patients have thalassemia minor from their donors, but one required a second BMT to achieve this state. Two of the four Diamond Blackfan Syndrome patients died of BMT-related complications. Two achieved normal hematopoiesis, one at the price of chronic graft vs host disease. Because of the excellent results of iron chelation in our patients, we question whether such patients with access to the state of the art transfusion-chelation programs should continue to be transplanted. This situation requires continuing evaluation.

Blood Transfusion↗
PubMed1993

Molecular detection of residual lymphoma cells in peripheral blood stem cell harvests and following autologous transplantation.

Twenty-seven patients with non-Hodgkin's lymphoma (NHL) have undergone peripheral blood stem cell (PBSC) harvesting for autologous transplantation (Tx). A molecular marker was found at presentation in 23/27 patients. Immunoglobulin heavy chain (IgH) or T cell receptor beta (TCR beta) rearrangements were detected by Southern blotting or the polymerase chain reaction (PCR) in 13 patients; PCR detected the bcl-2/JH fusion in 10 patients. Fifteen autologous PBSC transplants have been performed in 11 patients. In 5/11 patients, the marker was present in at least one PBSC collection (in four patients, every PBSC collection was positive). Survival data are available for nine patients (two early deaths); three patients relapsed and died (221 - 930 d), one is alive and in relapse (354 + d) and five are alive and in complete remission (330 - 1290 + d). These findings suggest that tumour cell contamination of PBSC harvests is not uncommon. Whether these cells are clonogenic and contribute to disease relapse remains to be elucidated. The presence of residual disease at the time of transplantation and the reappearance (or persistence) of marker positive cells post-transplantation both appear to be poor prognostic factors for disease-free survival.

Adult↗
PubMed1993

Optimization of conditioning therapy for leukemia prior to BMT. I. Optimal synergism between cyclophosphamide and total body irradiation for eradication of murine B cell leukemia (BCL1).

The doses of chemotherapy and radiotherapy and the sequence-dependent influence of CY administration and total body irradiation (TBI) on the eradication of murine B cell leukemia (BCL1) were investigated. Tumor-bearing BALB/c mice were treated with either CY followed by TBI (CY/TBI) or in the reverse (TBI/CY) at different time intervals after injection of 10(6) BCL1 cells. The presence of residual tumor cells after cytoreduction was assessed in secondary BALB/c recipients by monitoring leukemia-free survival. The anti-leukemic effect of CY followed by TBI was significantly better than TBI followed by CY. The survival of secondary adoptive recipients inoculated with 10(5) spleen cells obtained from mice treated with CY/TBI was 54% (57 of 105) compared with 25% (25 of 98) of recipients inoculated with 10(5) spleen cells obtained from mice treated with TBI/CY (p = 0.0001).

Animals↗
PubMed1993

Propantheline prevention of mucositis from etoposide.

Mucosal toxicity is dose limiting for etoposide. This may be related to the direct effects of etoposide on the mucosa. Twelve patients receiving etoposide 1800 mg/m2 as part of a myeloablative pre-transplant regimen were randomized to receive propantheline 30 mg or placebo orally every 6 h for six doses. Mucositis was less frequent (2 of 6 vs 5 of 6) and less severe (p = 0.05) in the propantheline arm. There were no differences in tumor response or survival between the two groups. Propantheline is an anticholinergic that causes xerostomia by decreasing salivation. Propantheline may reduce the salivary excretion of etoposide and could reduce its toxic effects on the mucosa. Propantheline is effective in reducing the incidence and severity of mucositis in patients receiving high-dose etoposide.

Adult↗
PubMed1993

Characterization of mixed chimerism in patients with chronic myeloid leukemia transplanted with T-cell-depleted bone marrow: involvement of different hematologic lineages before and after relapse.

We have characterized mixed chimerism (MC) in five patients with chronic myeloid leukemia (CML) who received transplants with T-cell-depleted bone marrow (BM) and who relapsed within 4 years after transplantation. To study the possible relation of MC with relapse, we purified different populations of leukocytes and analyzed their donor/recipient origin by a method based on polymerase chain reaction amplification of minisatellite DNA regions. Our results show that before relapse, all hematopoietic recipient cells are T cells, whereas monocytes, B, and natural killer (NK) cells are of donor origin. This observation does not appear to be specific for CML as similar results were found in two control patients with acute myeloid leukemia (AML). At the time of (CML) relapse, recipient granulocytes, monocytes, and erythrocytes appeared and progressively replaced the respective lineages of donor origin. No other lineages seemed to be involved as B cells and NK cells remained of donor origin and no significant changes in the number of recipient T cells were detected. In this respect relapse of CML after BM transplantation (BMT) seems not to be very different from the primary disease in chronic phase before transplantation. Furthermore, we conclude that after BMT, an association between mixed chimerism before relapse and the (CML) relapse does exist because both phenomena are consequences of T-cell depletion of the BM graft. However, this correlation might well be indirect as the MC caused by the recipient T cells appears to be independent of the one caused by the recurrent disease.

Adult↗