Engraftment of umbilical cord blood with glucose 6-phosphate dehydrogenase deficiency after double-unit unrelated cord blood transplantation

Abstract

The success of unrelated donor (URD) umbilical cord blood transplantation (UCBT) expands the potential pool of URD for hematopoietic SCT (HSCT). UCBT requires less stringent HLA matching than do other forms of HSCT, which does not apparently increase the frequency of graft failure or GVHD. Engraftment is related to total cell count per unit body weight. For adult recipients, double-unit UCB transplantation may be required for long-term engraftment. 1 Despite the infusion of two units of UCB, one unit finally engrafts. 2 A 47-year-old man with AML in second CR underwent a URD double-unit UBCT, with standard BU and CY as conditioning, and MTX and CYA as GVHD prophylaxis. Infection prophylaxis included ganciclovir, caspofungin, pentamidine, and lamivudine and isoniazid for chronic hepatitis B virus infection and past tuberculosis, respectively. He engrafted hematologically on day 25 with grade III acute GVHD of the skin and liver, associated with hemorrhagic cystitis. These complications were controlled with corticosteroids and mycophenolate mofetil. Serial peripheral blood DNA chimerism was monitored by semiquantitative PCR for polymorphic microsatellite loci as reported earlier. 3 The results showed engraftment initially of both UCB units, but ultimately of one unit only (Table 1). As one UCB unit came from a known glucose-6-phosphate dehydrogenase (G6PD)-deficient donor, serial assays of G6PD were performed. The results showed a gradual decrease of G6PD to the deficiency level, consistent with the results of DNA chimerism. 3 Therefore, the G6PD-deficient UCB had engrafted successfully, as shown both by DNA chimerism and the surrogate marker G6PD level.The incidence of G6PD deficiency in southern Chinese men is 4.8%, and all newborns are screened. Adult G6PD donors are allowed in most unrelated donor registries. 4 However, cord blood banks in some countries exclude voluntary units with known G6PD deficiency. 5 As shown in this case, G6PD-deficient UCB units are not at a disadvantage during engraftment, in the absence of oxidative stress. Exclusion of G8PD-deficient UCB donors therefore does not appear to be justified. Hence, we maintain our policy that G6PD deficiency should not be a consideration factor in selecting unrelated UBC for storage and donation. These observations are also in line with published results of HSCT from adult female donors heterozygous for G6PD deficiency, 6 where erythroid progenitors harboring the inactivated normal allele did not show any competitive engraftment disadvantage. In fact, stochastic skewing of X-chromosome inactivation might favor engraftment of HSC with the G6PD-deficient allele. 6 Finally, up to 10% of Chinese female newborns may be heterozygous for G6PD deficiency, which is not detectable by cord blood screening. It remains to be seen whether imbalanced skewing of X-chromosome inactivation might lead to G6PD deficiency after UCBT from female donors heterozygous for G6PD deficiency.

Glucose‐6‐phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks

“…Hematopoietic stem cells (HSCs) (from peripheral blood , bone marrow and umbilical cord blood ) from G6PD‐deficient donors have been successfully used for transplantation. Although data are limited, no adverse events related to granulocyte colony‐stimulating factor treatment are reported in G6PD‐deficient stem cell donors .…”

“…In most cases, the recipient converts to the G6PD status of the donor ; therefore, it is important to be aware that, following engraftment, a recipient of an HSC graft from a G6PD‐deficient donor will also be G6PD‐deficient. This observation leads some to advocate the use of serial measurements of G6PD activity following transplantation as an indicator of engraftment status . Additionally, when the HSC donor is a G6PD heterozygous female, the extent of G6PD deficiency in the recipient following engraftment can differ from that in the original donor, due to possible skewing of X‐inactivation at the time of engraftment.…”