Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

Little information is currently available on the outcome and the long-term restoration of immune function in infants with combined immunodeficiency and residual T cells (T þ CID) treated by BMT. We prospectively followed patients with T þ CID who received matched unrelated donor BMT at our center. Engraftment, immune reconstitution and transplant-related complications were recorded. Humoral and cellular immunity were evaluated. Ten patients with combined immune deficiency who had more than 1000 circulating T cells/ll were designated as having T þ CID. They were diagnosed at a mean age of 9.7 months and received a matched unrelated donor BMT at the mean age of 17.4 months. All 10 patients are alive and well at a mean of 110 months after transplant. All patients have evidence of full hemopoietic engraftment and robust immune function. We have shown here that matched unrelated donor BMT is highly effective in curing patients with T þ CID. This mode of treatment should be preferred for patients with T þ CID when a related identical donor is not available.

Section: Discussionmentioning

confidence: 99%

Matched unrelated bone marrow transplant for T+ combined immunodeficiency

Roifman

Somech

Grunebaum

2008

“…Histocompatibility testing for the identification of a matched unrelated stem cell donor is therefore a costly and time-consuming procedure. 6 Waiting in vain for an ideal donor may delay alternative donor transplants, for example, haploidentical HSCT or non-transplant strategies. Therefore, a more precise estimate at the initiation of the search of the probability of identifying a compatible donor could possibly improve the therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

The probability of identifying a 10/10 HLA allele-matched unrelated donor is highly predictable

Tiercy

Nicoloso

Passweg

et al. 2007

Self Cite

Identification of an unrelated HLA allele-matched hematopoietic stem cell (HSC) donor is a costly and time-consuming procedure. To improve search logistics, we have limited the search period to 6 months and have introduced a probability estimate of the chances of identifying a 10/10 HLA allele-matched donor. Probabilities were classified as high (>95%), intermediate (50%) and low (<5% chance) based on allele and haplotype frequencies. By analyzing 350 consecutive searches between 2002 and 2005 (1719 donors tested), the probability estimates turned out to be correct for 96% (high), 88% (low) and 56% (intermediate) patients. For searches with a high probability of success, at least one of the 10 most frequent haplotypes in Caucasoids was found in 69% of the patients, but in only 11% of the patients with a low-probability estimate (P<0.00001). Survival probability at 3 years was significantly higher for HSCT patients classified with a high-probability estimate when compared to patients in the intermediate/low-probability groups (74 vs 51 and 54% respectively, P=0.01). The same difference in survival probabilities was observed when only 10/10 matched unrelated HSCT patients were analyzed. In the intermediate-/low-probability groups, patients with alternative (haploidentical, autologous) or mismatched unrelated donors had similar survival estimates. Probability prediction is therefore feasible in the search process for unrelated donors and can guide the therapeutic strategy

“…[13][14][15][18][19][20][21] The presence of FH in patients also affects the probability and speed of identifying a matched UD. [22][23][24][25][26][27][28] It is essential to know the HLA distribution of each population at an allelic level in order to define whether a patient has a high or low probability of finding a matched donor. 27 Our group has previously shown that 30% of Northwest European patients became medically unfit during the search process and therefore did not receive a HSCT (which was unrelated to donor availability).…”

Section: Introductionmentioning

confidence: 99%

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Jöris

Lankester

Borne

et al. 2012

The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing Xgrade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of Xgrade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.