Bone marrow transplantation has resulted in life-saving sustained T cell reconstitution in many SCID infants, but correction of B cell function has been more problematic. patient, and showed that patients with IL7R, ADA and CD3 chain gene mutations can have normal B cell function post-transplantation with only host B cells. EH presented a statistical analysis of B cell function in published reports and showed that only a conditioning regimen that contained busulfan was significantly associated with better B cell function post-transplantation. The question is whether the risk of immediate and longterm toxicity in using busulfan is justified, particularly in SCID patients with DNA repair defects and in very young SCID newborns who will be detected by newborn screening. Keywords: Severe combined immunodeficiency, conditioning regimen, haematopoietic stem cell transplantation, B cell function, immunoglobulin therapy While bone marrow transplantation has resulted in life-saving sustained T cell reconstitution in most SCID infants,1 correction of B cell function has been more problematic.2 It has been suggested that the need for post-transplantation immunoglobulin (IG) replacement is due to a lack of donor B cell engraftment, leading some centers to use pre-transplant chemoablative conditioning in an effort to achieve this. However, data to support the efficacy of achieving this with Clinofibrate conditioning have been far from clear. Few studies have been published regarding longterm B cell function in patients with SCID who have received bone marrow transplants.3-15 A review from the RB of 19 reports from Europe and the United States published over the past two decades found that the percentage of survivors with B cell chimerism and/or function was higher and the percentage requiring IG replacement was lower at those Centers that used pre-transplant conditioning.2 However there Clinofibrate were substantial numbers of individuals requiring IG alternative whatsoever centers, so pre-transplant conditioning does not assurance development of B cell function.3;16 More importantly, survival rates were higher when neither pre-transplant conditioning nor post-transplantation immunosuppressive drugs were utilized for graft-versus-host disease (GVHD) prophylaxis.2;17;18 In most of the reviewed reports, there Clinofibrate was incomplete information about the underlying molecular problems that caused SCID in those subjects. This article contains the substance of a debate held in the annual meeting of the Primary Immunodeficiency Treatment Consortium (PIDTC) in April of 2012, where RB was the proponent of no conditioning and EH the proponent of conditioning, and the arguments posed within are given in the order they were offered. No Conditioning RB and her colleagues have recently published the results of a longitudinal study on B cell function in 125 surviving SCIDs according to their molecular type who received bone marrow transplants without pre-transplant chemotherapy or post-transplantation GVHD immunosuppressive medicines at her center over a 28 12 months period.19 Only 17 of the survivors received HLA-identical marrow, while the additional 104 received rigorously T cell-depleted haploidentical parental marrow. Table 1 shows the number and percentages with donor B cell chimerism and the number and percentages of individuals of each molecular type who currently require IVIG treatment. The molecular problems with the highest percentages of donor B cell chimerism were X-linked SCIDs, of which twenty-one (36%) experienced donor B cells, and ADA-Def SCIDs of which 6 (33%) experienced donor B cell chimerism, with smaller percentages of donor B Clinofibrate cell chimerism found among the additional molecular types. Eighty-nine (71%) of the individuals do not have donor B cell chimerism. However, only 61 (48.8%) of the 125 survivors require immunoglobulin (IG) alternative therapy. Therefore, 28 of the survivors without B cell chimerism do not require IG alternative. Sixty-two percent of those requiring IG alternative are X-linked SCIDs; 38 of the 58 X-SCID individuals are currently receiving it and Clinofibrate 37 of them do not have KLRK1 B cell chimerism. Additional molecular types with a high percentage receiving IG alternative are RAG-Def SCIDs (83%) and autosomal recessive SCIDs of unfamiliar molecular type (73%). By contrast, only 1 1 (6%) of the 17 individuals with IL7R-Def SCID, 4 (22%) of the.