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Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) occur in patients receiving immunosuppressive drugs for autoimmune diseases; however, their clinicopathological and genetic features remain unknown. In the present study, we analysed 67 patients with OIIA-LPDs, including 36 with diffuse large B-cell lymphoma (DLBCL)-type and 19 with Hodgkin lymphoma (HL)-type. After discontinuation of immunosuppressive drugs, regression without relapse was achieved in 22 of 58 patients. Spontaneous regression was associated with Epstein-Barr virus positivity in DLBCL-type (P = 0·013). The 2-year overall survival and progression-free survival (PFS) at a median follow-up of 32·4 months were 92·7% and 72·1% respectively. Furthermore, a significant difference in the 2-year PFS was seen between patients with DLBCL-type and HL-type OIIA-LPDs (81·0% vs. 40·9% respectively, P = 0·021). In targeted sequencing of 47 genes in tumour-derived DNA from 20 DLBCL-type OIIA-LPD samples, histone-lysine N-methyltransferase 2D (KMT2D; eight, 40%) and tumour necrosis factor receptor superfamily member 14 (TNFRSF14; six, 30%) were the most frequently mutated genes. TNF alpha-induced protein 3 (TNFAIP3) mutations were present in four patients (20%) with DLBCL-type OIIA-LPD. Cases with DLBCL-type OIIA-LPD harbouring TNFAIP3 mutations had shorter PFS and required early initiation of first chemotherapy. There were no significant factors for spontaneous regression or response rates according to the presence of mutations. Overall, OIIA-LPDs, especially DLBCL-types, showed favourable prognoses.

Umbilical cord blood transplantation (CBT) is widely accepted, but one critical issue for adult patients is a low engraftment rate, of which one cause is haemophagocytic syndrome (HPS). We aimed to identify the contribution of HPS to engraftment failure after CBT, following preparative regimens containing fludarabine phosphate, in 119 patients (median age, 55 years; range; 17-69 years) with haematological diseases. Graft-versus-host disease prophylaxis comprised continuous infusion of a calcineurin inhibitor with or without mycophenolate mofetil. Of the 119 patients, 20 developed HPS within a median of 15 d (cumulative incidence; 16.8%) and 17 of them did so before engraftment. Donor-dominant chimaerism was confirmed in 16 of 18 evaluable patients with HPS. Despite aggressive interventions including corticosteroid, ciclosporin, high-dose immunoglobulin and/or etoposide, engraftment failed in 14 of 18 patients. Of these 14 patients, four received second rescue transplantation and all resulted in successful engraftment. Overall survival rates significantly differed between patients with and without HPS (15.0% vs. 35.4%; P < 0.01). Univariate and multivariate analysis identified having fewer infused CD34(+) cells as a significant risk factor for the development of HPS (P = 0.01 and 0.006, respectively). We concluded that engraftment failure closely correlated with HPS in our cohort, which negatively impacted overall survival after CBT.

We reviewed the medical records of 123 adult reduced-intensity cord blood transplantation (RI-CBT) recipients to investigate the clinical features of graft failure after RI-CBT. Nine (7.3%) had graft failure, and were classified as graft rejection rather than primary graft failure; they showed peripheral cytopenia with complete loss of donor-type haematopoiesis, implying destruction of donor cells by immunological mechanisms rather than poor graft function. Three of them died of bacterial or fungal infection during neutropenia. Two recovered autologous haematopoiesis. The remaining four patients underwent a second RI-CBT and developed severe regimen-related toxicities. One died of pneumonia on day 8, and the other three achieved engraftment. Two of them died of transplant-related mortality, and the other survived without disease progression for 9.0 months after the second RI-CBT. In total, seven of the nine patients with graft failure died. The median survival of those with graft failure was 3.8 months (range, 0.9-15.4). Graft failure is a serious complication of RI-CBT. As host T cells cannot completely be eliminated by reduced-intensity preparative regimens, we need to be aware of the difficulty in differentiating graft rejection from other causes of graft failure following RI-CBT. Further studies are warranted to establish optimal diagnostic and treatment strategies.

The impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft-versus-host disease (GVHD) and graft failure after reduced-intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II-IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA-matched donors, 44% in those with one-locus-mismatched donors, and 50% in those with two- to three-loci-mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II-IV aGVHD (P=0.01), chronic GVHD (cGVHD) (P=0.05) and graft failure (P=0.033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two- to three-loci-mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one-locus-mismatched RICT (51%) and HLA-matched RICT (48%) (P