ALLOGENEIC MARROW GRAFTS FROM UNRELATED DONORS WITH CONGENITAL PERICENTRIC INVERSION OF CHROMOSOME 9

Abstract

Allogeneic marrow transplantation from related donors with congenital chromosomal abnormalities has been reported (Barquinero et al, 1995). A higher incidence of graft failure was encountered in Down's syndrome and Fanconi syndrome heterozygotes. We describe two cases of allogeneic bone marrow transplantation from unrelated donors with pericentric inversion of chromosome 9. Case 1. A 44-year-old woman underwent allogeneic bone marrow transplantation for chronic myeloid leukaemia in myeloblastic crisis from a human leucocyte antigen (HLA)-matched unrelated male donor, after high-dose cyclophosphamide and fractionated total body irradiation, in 1993. She received non-manipulated bone marrow with a total of 2·1 × 108 mononuclear cells/kg. Myeloid engraftment was attained by d +24. However, she continued to have poor erythroid and platelet recovery requiring frequent transfusions. Two months after transplant, her white blood cell (WBC) count decreased to 1·3 × 109/l and the platelet count to 10 × 109/l. Repeat bone marrow examination revealed hypocellular marrow consistent with graft failure. Cytogenetic studies of the bone marrow revealed donor male phenotype of 46 XY, inv(9). Granulocyte colony-stimulating factor (G-CSF) was started and her blood counts gradually recovered 4 weeks later. The patient is alive with normal blood counts and no evidence of leukaemic recurrence, 6 years later. Case 2. A 23-year-old man, diagnosed with severe aplastic anaemia in 1989, was initially treated with antithymocyte globulin with no response. He underwent allogeneic bone marrow transplant from an HLA-matched unrelated female donor in July 1990 after conditioning with high-dose cyclophosphamide, cytarabine arabinoside (ara-C), methylprednisolone and total body irradiation. A total of 4·68 × 108 mononuclear cells/kg were harvested and T-cell depleted prior to transplantation (Hsu et al, 1987). Xomazyme, an anti-CD5-ricin A chain immunotoxin, and methylprednisolone were used for graft-versus-host disease (GVHD) prophylaxis. He developed grade II acute GVHD on d +28 that was treated successfully with a brief course of high-dose methylprednisolone. The patient had poor engraftment with WBC 1·5 × 109/l on d +56; WBC 1 × 109/l and platelets 8 × 109/l on d +75; WBC 1·9 × 109/l and platelets 10 × 109/l on d +125. Repeat bone marrow biopsy was hypocellular with overall cellularity < 10%. Cytogenetic study of the bone marrow showed 46, XX, inv(9). He received a course of antithymocyte globulin in November 1990 without response. G-CSF was started in January 1991 which resulted in a WBC increase to 11 × 109/l, a Hb level of 8·7 g/dl, and a platelet level of12 × 109/l. Unfortunately, the patient developed cytomegalovirus pneumonia and retinitis. Two months later, the patient succumbed shortly after diagnosis from post-transplant high-grade immunoblastic lymphoma in the brain. In recent years, the incidence of constitutional chromosomal abnormalities in apparently normal individuals has increased. Pericentric inversion of chromosome 9 occurs in about 1–1·5% of the normal population (Tawn & Earl, 1992; Lamb et al, 1994). Although it is generally regarded as a normal variant, it has been implicated in infertility, recurrent abortion and psychiatric disorders (Uehara et al, 1992; Daya, 1994; Inayama et al, 1997). Despite theprevalent occurrence, there has not been any report of bone marrow transplantation involving these individuals either as a donor or recipient. To our knowledge, this is the first report of allogeneic bone marrow transplantation from donors with constitutional inv(9). Persistent cytopenia after bone marrow transplantation is common and may be as a result of a variety of causes, such as inadequate stem cell dosage, purging, graft rejection, antibiotics, intercurrent viral infection, etc. It is conceivable that graft failure of these two cases is simply coincidental. Alternatively, it is possible that donor marrow with constitutional inv(9) may be associated with delayed haematopoietic recovery, which has also been described in allografts from donors with Down's syndrome and Fanconi anaemia heterozygotes (Barquinero et al, 1995). Further studies and case reporting are required to confirm our observation.