Stem Cell Transplantation from Mismatched Related Donors for Paediatric Haematological Disorders : The Hospital for Sick Children, Toronto, Experience.

Between June 1994 and December 2003, 31 patients with haematological disorders presenting at the Hospital for Sick Children, Toronto, Canada, received a stem cell transplant (SCT) from a mismatched related donor. Diagnoses included ALL (15), AML (10), CML (1), JMML (1), SAA (2), de novo MDS (1) and Fanconi anaemia (1). Patients were aged between 0.9 to 17.8 years (mean 8.5 years). There were 20 males and 11 females. HLA typing included A, B and DRB1 on all patients (Class 1 alleles by low resolution molecular technique and Class 2 by high resolution technique). 22 patients had 1 major mismatch and 9 had 2–3 major mismatches. The source of stem cells was bone marrow in 15 patients (mean total nucleated cell dose 4.44 x 10⁸/kg, range 1.89–6.63), peripheral blood (PBSC) in 15 patients (mean CD34 dose 11.80 x 10⁶/kg, range 3.19–42.18) and one patient received both BM and PBSC. Of those who received PBSC, 9 had CD34 selection, 3 had CD34 selection and T-cell depletion, and 3 received an unmodified product. Conditioning regimens included cyclophosphamide and total body irradiation (TBI) (15), etoposide and TBI (6), busulfan and cyclophosphamide (6), etoposide and cyclophosphamide (1), fludarabine, cyclophosphamide and TBI (1), fludarabine and cyclophosphamide (1) and fludarabine, melphalan and thiotepa (1). Graft versus host disease (GvHD) prophylaxis included combinations of cyclosporine A, methotrexate, anti-thymocyte globulin and methylprednisolone. There was one primary graft failure and 3 secondary graft failures. Mean time to neutrophil engraftment was 17 days (range 9–36). The incidence of acute and chronic GvHD was 48% and 51% respectively. Of the 31 patients, 15 are alive (12 in complete remission (one of these with a secondary brain tumour) and 3 with relapsed disease) and 16 are dead (3 of relapsed progressive disease, 12 from transplant related mortality (TRM - 9 of these were in CR) and in one the cause is not known). Three year actuarial OS and EFS for the entire group were 50±9% and 45±9%, OS and EFS for those matched at 5/6 loci were 56±11% and 44±11% and OS and EFS for 3/6 and 4/6 matched were 38±16% and 36±16%. The mean follow-up time for survivors is 5.6 years (range 11.6 months to 9.7 years). In this series, there was no significant difference in survival when comparing BM vs. PBSC harvests; in one vs. 2–3 mismatch donors; and in the presence vs. absence of acute or chronic GvHD. These results confirm the feasibility and efficacy of using mismatched related donors for paediatric haematological disorders. Steps should be taken to decrease the TRM to achieve a better survival rate.