Are UC blood transplants prone to developing leukemia

In this issue of Cytotherapy, Nagamura-Inoue and colleagues from the Tokyo Cord Blood Bank describe AML occurring in four recipients of unrelated cord blood (UCB) transplants, two with a primary diagnosis of AML and two with lymphomas. The AML occurred 7 16 months after two myeloablative and two non-myeloablative transplants. The donor origin of the leukemia was confirmed by fluorescent interphase somatic hybridization (FISH) Y-probe and by small tandem repeat (STR) DNA analysis. Leukemia occurring in donor hematopoietic cells was first observed by Fialkow et al. in 1971 [1]. It is considered a rare occurrence after allogeneic BMT and to date has been reported in only 24 BM transplants and one PBSC transplant recipient [2]. This is probably an underestimate of the true risk of post-transplant donor-acquired leukemia (DL), because of under-investigation of post-transplant relapse and under-reporting and the fact that patients may develop other complications (including relapse of the recipient disease) before donor-derived leukemia can develop. There are no known risk factors leading to DL. It occurs after any type of transplant, ablative or nonablative, with family or unrelated donors, with or without GvHD, in recipients with all types of primary diagnosis of malignancy and occasionally in non-malignant disorders. The mechanism is unknown; the rarity of the event suggests that more than one risk factor is required, which could include a genetic predisposition in the donor together with a facilitatory environment in the recipient. It has been suggested that the post-transplant marrow stromal microenvironment (which remains of recipient origin after SCT) together with an inflammatory cytokine milieu is permissive for leukemogenesis [3]. There have been no reports of the donors themselves developing leukemia, an important fact when considering UCB transplants and the anxiety that could be caused for the family of a healthy child whose cord blood developed leukemia in a recipient. The question raised by this latest report is whether DL is more common after UCB transplants. UCB stem cells home less efficiently to the marrow: perhaps they are more prone to leukemic transformation if they lodge in extramedullary sites? The Tokyo report is the first to provide a true denominator: four cases out of 478 transplanted units gives an incidence of a little less than 1%. However, of an estimated 6000 UCB transplants performed world-wide there have been only five reports of DL, giving a crudely estimated incidence of 0.08%. This statistic can be compared with 25 reports of DL following other stem cell transplants: since 1972 it is estimated that more than 100 000 allotransplants have been performed world-wide, giving a crude estimate of DL of B0.02%. While these figures suggest an increased risk of DL following UCB transplants, in the absence of better data it is safer to assume that there is no substantial evidence that UCB transplants result in more DL. Nevertheless it pays to be vigilant: providers of UCB or unrelated adult stem cells could mandate that chimerism is performed on leukemia occurring or recurring after SCT. Frustratingly, because of the rarity of the event, the mechanisms surrounding the occurrence of DL are likely to remain obscure.