T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency (original) (raw)
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Bone Marrow Transplantation, 1997
the mature T cells from the donated marrow. 2 This approach has subsequently been successful in over half of the transplanted children with SCID. Graft failure is much Bone marrow transplantation is the only curative treatment for children with severe combined immunodefi-less common in children than in older leukaemic patients given similarly treated marrow perhaps because children ciency (SCID). In the absence of an HLA-identical sibling, haploidentical parental donor marrow can be used with SCID lack the alloreactive immune responses that mediate graft rejection. 3-5 provided it is depleted of T cells to prevent otherwise inevitable GVHD. Campath 1M has been successfully T cell depletion has been accomplished by a variety of methods including physical separation with soya bean lec-used for this procedure in several centres. In our centre 17 SCID patients plus one with combined immunodefi-tin and sheep erythrocyte rosetting, 6 as well as immunochemical methods using monoclonal antibodies to lymphocyte ciency (CID) were transplanted with Campath 1M T cell-depleted bone marrow. Progenitor cell recovery, surface antigens, such as Campath 1M in vitro and Campath 1G added to the bag of donor marrow or infused in before and after T cell depletion, was monitored using granulocyte-macrophage colony-forming cell assays vivo. 7, 8 We describe a series of 18 T cell-depleted transplants carried out in our BMT centre over the past 8 years, (GMCFU) and CD34 analysis. The numbers of GMCFU/kg transplanted correlated with engraftment during which time the method of marrow manipulation during T cell depletion was changed in an attempt to conform and survival post-transplant and monitoring CD34 + cell numbers in the T cell-depleted marrow pretransplant with other European centres who mainly used physical methods of T cell depletion. Unfortunately this change may be an additional indicator of successful engraftment. Use of a buffy coat marrow preparation appeared to contribute to several failures of engraftment. We therefore attempted to identify markers that would pre-with restriction of the number of T cells to Ͻ5 × 10 5 /kg was associated with graft failure in four and death in dict lymphoid engraftment and our results suggest that the number of both CD34 + cells and GMCFU infused per kg five of eight children, probably because too few stem cells were infused. T cell depletion of a mononuclear cell correlates with sustained engraftment and survival following T cell-depleted donor marrow transplantation in preparation of donor marrow with no arbitrary ceiling of infused T cells is highly effective at preventing clini-patients with SCID. cally important GVHD and cured nine out of 10 children transplanted with such material.
Neonatal bone marrow transplantation for severe combined immunodeficiency
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2001
To evaluate outcome following neonatal bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) when there is a family history of a previously affected sibling, and to compare results with those published for in utero BMT. A retrospective review of cases referred and transplanted between 1987 and 1999, focusing on infectious and graft versus host disease (GvHD) complications after BMT, and T and B lymphocyte function. Thirteen patients received 18 stem cell transplants: four whole marrow, one cord blood, 10 parental T cell depleted (TCD) haplo-identical, and three TCD unrelated donor BMT. Nine were conditioned with busulphan and cyclophosphamide. All are alive and well (six months to 11.5 years after BMT). Six had grade I-II acute GvHD and two chronic GvHD (now resolved). Three had a top up BMT for poor T cell function, one had a third BMT for graft failure and chronic GvHD, and one had a third BMT for graft failure. Twelve have good in vitro proliferation to T cell mitogens, and all have normal serum IgA levels. Three receive intravenous immunoglobulin; for one of these, it is less than one year since BMT. Nine are above the 2nd centile, and 10 of 12 old enough to be assessed have normal neurodevelopment. These results are better than those published for in utero BMT for SCID. Early postnatal BMT should be the preferred option in neonatal SCID.
Immunologic Research, 2009
We review clinical outcome and immune reconstitution in a consecutive series of 74 infants with severe T cell immunodeWciency who received hematopoietic cell transplantation (HCT) from January 1991 to May 2003. Fifty-three patients (71.6%) are alive. Results were signiWcantly better for recipients of HCT from HLA-matched related donors (100% survival) and unrelated donors (86.4%) than from mismatched related donors (51.6%). A detailed analysis of immune reconstitution and clinical status was performed in 49 surviving patients, most of which have attained robust T and B cell reconstitution and are in very good clinical conditions. No cases of late deaths or of chronic graft-versus-host disease (GvHD) have been observed. However, infections and autoimmunity at >1 year after HCT have been observed in a signiWcant number of patients. Persistence of a low number of circulating naive T cells and long-term requirement for intravenous immunoglobulin were associated with a higher incidence of clinical events.
Transplantation outcomes for severe combined immunodeficiency, 2000-2009
The New England journal of medicine, 2014
The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth. We collected data retrospectively from 240 infants with SCID who had received transplants at 25 centers during a 10-year period (2000 through 2009). Survival at 5 years, freedom from immunoglobulin substitution, and CD3+ T-cell and IgA recovery were more likely among recipients of grafts from matched sibling donors than among recipients of grafts from alternative donors. However, the survival rate was high regardless of donor type among infants who received transplants at 3.5 months of age or younger (94%) and among older infants without prior infection (90%) or with infection ...
Clinical Immunology and Immunopathology, 1984
Two infants with immunodeficiency with predominant T-cell defects received transplants of HLA-identical bone marrow cells along with thymopoietin pentapeptide (TP-5) treatment and no prior immunosuppressive therapy. Both patients achieved durable engraftment with early reconstitution of cell-mediated immunity. The study of cell surface antigens with monoclonal antibodies (MoAb) revealed that the early appearance of T-cell subsets defined by 0KT4 and OKT8 MoAb occurred. Neither of the patients showed any signs or symptoms of graft versus host disease over a l-year period. This experience suggests that patients with T-cell deficiency who do not benelit from thymic hormones alone can be successfully treated by bone marrow transplantation. The association of TP-5 with bone marrow transplantation seems to induce an early and stable reconstitution and to protect against fatal post-transplant infection.
Biology of Blood and Marrow Transplantation, 2020
Results: Donors were haploidentical donor (n=84, 83%), MUD/ MFD (n=9, 9%) and MMFD/MMUD (n=8, 8%). 94% received conditioning. Thirteen (12%) patients had aGvHD, of whom 3 had grade III-IV. None had cGvHD. The cause of death changed from predominantly infection (18/25, 72%) in CAMPATH-IM and CD34-S to non-infectious causes in all 6 deaths in CD3/ CD19 and ab-TCD. Analysis by TCD methods revealed a 5-year OS of 58% (95% CI, 40-73%) for CAMPATH-1M, 68% (49-81%) for CD34-S, 69% (22-91%) for CD3/CD19 TCD and 83% (61-93%) for (ab-TCD (p=0.24). Age was a significant predictor of OS for non-SCID PID (p=0.02). The corresponding EFS was 46% (29-62%) for CAMPATH-1M, 47% (30-62%) for CD34-S, 69% (95% CI, 22-91%) for CD3/CD19 TCD and 83% (61-93%) for ab-TCD (p=0.04) (Fig 1B) The CI of graft failure reduced significantly, from 29% (14-61%) for CAMPATH-1M, to 19% (95%CI, 8-45%) for CD34-S, 17% (2-18%) for CD3/CD19 TCD and none had graft failure in ab-TCD (p=0.002) (Figure 1C). CD4+ lymphocytes were significantly higher in CD34-S at months 4 (p=0.02), 5 (p=0.01), and 6 (p=0.006) post-HCT and at month 4 (p=0.04) post-HCT in ab-TCD when compared to CAMPATH-1M (Fig 1D). The median donor myeloid chimerism at last follow-up was higher in newer TCD; 100% (range, 0-100%) for ab-TCD, 93% (0-100%) for CD3/CD 19 depletion, 6% (0-49%) for CD34-S, 20% (0-100%) for CAMPATH-1M (p<0.001). There was no significant difference in donor T-lymphocyte chimerism between TCD. Conclusions: Outcomes after CD3+TCR ab/CD19+ depletion are superior to previously used TCD methods. In an experienced centre it is a safe alternative procedure and enables a wide spectrum of PID to be transplanted. The result has led to evolution of donor hierarchy in our centre.
Blood, 2001
Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in T-lymphocyte engraftment and correction of immune dysfunction but not in full hematopoietic engraftment. A case of a 17-month-old girl with adenosine deaminase (ADA) deficiency SCID in whom full hematopoietic engraftment developed after BMT from her HLAidentical sister is reported. No myeloablative or immunosuppressive therapy or graft-versus-host disease (GVHD) prophylaxis was given. Mild acute and chronic GVHD developed, her B-and T-cell functions became reconstituted, and she is well almost 11 years after BMT. After BMT, repeated studies demonstrated: (1) Loss of a recipient-specific chromosomal marker in peripheral blood leukocytes (PBLs) and bone marrow, (2) conversion of recipient red blood cell antigens to donor type, (3) conversion of recipient T-cell, B-cell, and granulocyte lineages to donor origin by DNA analysis, and (4) increased ADA activity and metabolic correction in red blood cells and PBLs. (Blood. 2001;97:809-811)