Allogeneic marrow transplantation for aplastic anaemia associated with dyskeratosis congenita

Abstract

Eight patients with aplastic anaemia associated with dyskeratosis congenita received allogeneic marrow grafts from either HLA-identical siblings (six patients) or HLA-matched unrelated donors (two patients). Patients who received marrow from HLA-identical siblings were conditioned with cyclophosphamide (140-200 mg/kg), with or without antithymocyte globulin. Patients who received unrelated donor marrow were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (1200 cGy). The six patients who survived for >2 weeks following transplant all had haematological evidence of engraftment, and all three patients who survived for at least a year following transplant recovered normal haematological function. Three patients died with respiratory failure and pulmonary fibrosis at 70 d. 8 years and 20 years posttransplant; three patients died during the neutropenic period of invasive fungal infections; one patient died on day 44 of refractory acute graft-versus-host disease; and one patient remains alive 463 d following transplant. The surviving patient recently underwent surgical resection of a Dukes' stage C rectal carcinoma diagnosed 14 months posttransplant. The aplastic anaemia associated with dyskeratosis congenita can be successfully treated by allogeneic bone marrow transplantation; however, this approach does not reverse the other systemic manifestations of the syndrome. The pathogenesis of the intestinal lung disease observed in dyskeratosis congenita patients following marrow transplantation is not understood.

Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita

“…Various regimens have been examined, but there is not yet a commonly accepted standard. 9,12,14,[18][19][20][21][22][23][24][25][26][27][28][29][30] Table 3 summarizes the reported experience of HCT for patients with DC using reducedintensity conditioning, including specifics of donors, regimens and outcomes. Kaplan-Meier analysis revealed that overall cumulative survival was 65%, with related donor recipients having better survival compared with unrelated donor transplants (91 vs 30%, respectively, P ¼ 0.05).…”

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure

“…Previous reports (Table 3) have described progression of the clinical signs of DKC after transplantation, which was indistinguishable from the natural course of disease. [8][9][10][11][20][21][22][23] In our series, all patients except one received low intensity conditioning regimens. The conditioning protocol was different across different centers.…”

“…However, the tolerability of the conditioning regimen is always limited by the increased risk of developing significant tissue injury as a result of irradiation and chemotherapy due to inherited defects in genome maintenance. [18][19][20][21][22][23] This hypersensitivity to irradiation and chemotherapy translated into poor survival of patients after SCT, using conventional myeloabaltive conditioning. 20,21 Short-term transplant-related complications are not uncommonly observed in patients with DKC in the setting of allo-HSCT.…”

“…Longer follow-up is still needed to determine if long-term toxicity is also reduced when using such regimens. 10,12,18,[22][23][24]35 …”

Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation

“…Results of allogeneic bone marrow transplantation in these patients have been relatively poor due to early and late complications. [6][7][8][9][10] We describe the effect of bone marrow transplantation for aplastic anemia in two siblings with dyskeratosis congenita from a single donor. The other brother of these two siblings had died due to bone marrow failure and dyskeratosis congenita previously.…”