SummaryUmbilical cord blood has become a valuable alternative source of haematopoietic stem cells for allogeneic transplantation. However, largely because of the impact of cell dose on engraftment, risk of transplant-related mortality and survival, progress in the field has been largely restricted to children. Nevertheless, substantial clinical experience with umbilical cord blood transplantation clearly establishes its safety and effectiveness in young patients with a variety of malignant and non-malignant diseases. Although less well established in adults, new strategies are now being explored to address the obstacle of cell dose. This article reviews the state of the art and future directions with umbilical cord blood as a source of haematopoietic stem cells for transplantation in both children and adults.

Cells from Fanconi anemia (FA) patients are hypersensitive to alkylating agents and radiation traditionally used as conditioning regimens for marrow cell transplantation, and patients experience serious toxicities. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning. Here, we report the results in 43 FA patients who received marrow transplantation from HLA-matched related donors (37 siblings and 6 other relatives). Conditioning consisted of 15 mg CY/kg/day for 4 days along with Mesna. Methotrexate and cyclosporine were given for graft-versus-host disease (GVHD) prophylaxis. Forty patients (93%) are alive with a median follow-up of 3.7 (range 0.6 to 7.9) years. One patient with primary graft failure was successfully retransplanted. Three of 4 patients with late graft failures were retransplanted, and 2 of those are alive; 1 died before a second marrow graft. Twelve patients including 3 with rejection had cytogenetic abnormalities in their marrow cells before transplantation. Acute grade II-III and chronic GVHD (aGVHD, cGVHD) were seen in 17% and 28.5% of patients, respectively. These results confirm and extend our previous observations that conditioning with 60 mg CY/kg allows for sustained engraftment of HLA-matched related marrow grafts in most FA patients and is associated with low toxicity, low incidences of aGVHD and cGVHD, and excellent long-term survival.

The hematopoietic cell transplantation specific comorbidity index (HCT-CI) has been recently proposed to predict the probability of nonrelapse mortality (NRM) and overall survival (OS) in allogeneic HCT recipients while taking into account any pretransplant comorbidity. We tested the validity of the HCT-CI in a cohort of 373 adult HCT recipients (184 matched-related donor and 189 unrelated umbilical cord blood) who received a myeloablative (N = 150) or nonmyeloablative (N = 223) conditioning regimen. HCT-CI scores of 0, 1, 2, and > or =3 were present in 58 (16%), 56 (15%), 64 (17%), and 195 (52%) patients, respectively. Pulmonary conditions were the most common comorbidity. Cumulative incidence of NRM at 2 years was 10%, 20%, 24%, and 28% for HCT-CI scores of 0, 1, 2, and > or =3, respectively (P = .01). The corresponding probability of OS at 2 years was 72%, 67%, 51%, and 48%, respectively (P < .01). On multivariate analyses adjusted for recipient age, disease risk, donor source, and conditioning regimen intensity, the relative risks for NRM for HCT-CI scores of 1, 2, and > or =3 (compared to a score of 0) were 2.0 (95% confidence intervals, 0.8-5.3), 2.6 (1.0-6.7), and 3.2 (1.4-7.4), respectively. The risks for overall mortality were 1.2 (0.6-2.1), 2.0 (1.1-3.4), and 2.1 (1.3-3.3), respectively. In subgroup analyses, the HCT-CI score did not consistently predict NRM and OS among different donor sources and conditioning regimens. The HCT-CI, although a useful tool for capturing pretransplant comorbidity and risk-assessment, needs to be further validated prior to adopting it for routine clinical use.

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Summary Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen‐matched related donors. Methotrexate and cyclosporine were given for graft‐versus‐host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2–3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0·001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44–58) months and 16 (3–52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients.