Summary:Among 551 consecutive recipients of allogeneic bone marrow transplants, 451 survived more than 3 months and were evaluated for chronic graft-versus-host disease (GVHD). Most of the donors were HLA-identical siblings or parents (n = 334). Patients with HLA-mismatched donors (n = 30) and matched unrelated donors (MUD) (n = 87) were also included in the study. In the analysis of all patients, the 5-year cumulative incidence of chronic GVHD was 45%. We analysed 34 risk factors. High recipient age was the single most important risk factor (P Ͻ 0.001). Other significant risk factors in multivariate analysis were: acute GVHD grades I-IV (P Ͻ 0.001), immune female donor to male recipient (P = 0.006) and chronic myelogenous leukaemia (CML), compared with all other diagnoses (P = 0.014). The cumulative 5-year incidence of chronic GVHD, with no significant risk factors present, was 9%, 29% with one risk factor, 53% with two, 68% with three and 75% with all four risk factors present. In patients with HLAidentical sibling donors and GVHD prophylaxis consisting of a combination of methotrexate (MTX) and cyclosporin A (CsA) (n = 208), increasing recipient age (P Ͻ 0.001) and CML (P = 0.007), were found to be significant risk factors for chronic GVHD. Finally, a multivariate analysis in recipients of bone marrow from unrelated donors (n = 89) showed recipient age alone (P = 0.006) to be significantly associated with chronic GVHD.

Engraftment was achieved in 43/45 (95%) recipients of peripheral blood stem cells (PBSC) from HLA-compatible unrelated donors (n = 45), compared to all 45 patients in matched controls receiving bone marrow and 14/18 (78%) recipients of CD34-selected PBSC (P < 0.01). The time to reach ANC >0.5 x 10(9)/l was a median of 16 days in the PBSC and CD34 groups, compared to 20 days in the bone marrow controls (P < 0.001 vs PBSC). The time to reach platelets >50 x 10(9)/l was a median of 23 days in the PBSC group and 24 days in the CD34 group, which was significantly faster than 29 days in the bone marrow controls (P < 0.01). Acute GVHD grades II-IV developed in 30% in the PBSC group, 20% in the recipients of bone marrow and 18% in the CD34 group. The corresponding figures for chronic GVHD were 59%, 85% and 0% (P < 0.01) in the three groups, respectively. The probability of non-relapse death was 27% in the recipients of PBSC, 21% in the bone marrow controls and 60% in the CD34 group (NS). The 2-year leukaemia-free survival was 46% in the PBSC group, 41% in the bone marrow group and 25% in the CD34 group (NS).

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HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P &lt; .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease–donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy–based Haplo-HCT vs MSD using calcineurin inhibitor–based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

To assess the impact of spleen status on engraftment and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil and platelet engraftment were 15 vs. 18 days and 22 vs. 24 days for the SP and NS groups, respectively (p<0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds of days +14 and +21 neutrophil and day +28 platelet engraftment were 3.26, 2.25, and 1.28 for splenectomy, and 0.56, 0.55, and 0.82 for splenomegaly groups compared to normal spleen (p<0.001), respectively. Among patients with splenomegaly, use of peripheral blood grafts improved neutrophil engraftment at day +21, and CD34+ cell dose >5.7x106/kg improved platelet engraftment at day+28. After adjusting variables by Cox regression, the incidence of graft-versus-host disease (GVHD) and overall survival were not different among groups. Splenomegaly is associated with delayed engraftment while splenectomy prior to HCT facilitates early engraftment without impact on survival.

10 mononuclear cells from the whole thoracic and lumbar vertebral column. With a mean fraction of CD34-positive cells of 2.1 ؎ 0.3%, recovery and purity were not affected by site of sample, temperature or donor age. In contrast, the CD34-positive fraction in spleen preparations was 0.41 ؎ 0.06%. When analyzing the number of colony-forming units (CFU-GM, BFU-E and CFU-GEMM), we found no significant differences between cadaveric bone marrow and bone marrow aspirates from living donors. However, cells harvested from the spleen gave significantly fewer CFUs than did bone marrow from living donors. We conclude that bone marrow from cadaveric donors can be harvested and procured with a high degree of viability and good function. With an appropriate technique of harvesting and procurement, it seems feasible to recover enough stem cells for transplantation.

Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P = .0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P = .001), and cGVHD (HR, .32; 95% CI, .19 to .54; P < .001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P = .0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P = .0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P = .0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P = .0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.

Summary:who become exposed to the virus by a marrow graft from a CMV positive donor or by blood products. Several randomized trials of the effectiveness of CMV hyperimmune A randomized multicentre study was conducted to evaluate the effect of anti-CMV hyperimmune globulin globulin or plasma in the prevention of CMV infection and disease in BMT patients have given conflicting results. 4,6 in the prophylaxis of CMV infections in CMV seronegative allogeneic BMT patients who received a transplantWe have carried out a randomized multicentre trial to study the effectiveness of intravenous CMV hyperimmune globufrom a seropositive donor or who had received blood products unscreened for CMV during the treatment lin in the prevention of CMV infection and disease in seronegative bone marrow transplant recipients who before BMT. Twenty-eight patients were included in the study. Thirteen were randomized to receive and 15 not received a transplant from a seropositive donor or had been given blood products unscreened for CMV before BMT. to receive intravenous CMV hyperimmune globulin. A dose of 0.4 g/kg of immunoglobulin was given on day ؊8 and 0.2 g/kg on days ؊1, ؉7, ؉14, ؉21, ؉28, ؉35, ؉42, ؉56 and ؉70 in relation to the day of transplanPatients and methods tation. Among the 15 patients not given immunoglobulin CMV was isolated in three, and two of them developed Patients clinical CMV disease. In addition, one more patient Twenty-eight CMV seronegative patients treated with allodeveloped CMV antibodies without virus isolation. In geneic BMT were included in the study. All the patients five of the 13 patients given immunoglobulin the virus were CMV seronegative as determined by ELISA-based could be isolated, and four of them developed CMV distechniques at each centre 3-4 weeks prior to the transplanease. One additional patient showed seroconversion but tation. They either received a transplant from a CMV serono other findings of CMV infection. The incidence of positive donor (25 patients), or the transplant was from a acute and chronic GVHD was similar in the two arms.seronegative donor but blood transfusions unscreened for There was no significant difference in survival. In con-CMV had been given during the treatment before the transclusion, the present results do not indicate a beneficial plantation (three patients). The patients were randomized effect of CMV hyperimmune globulin infusions in the to receive (n ϭ 13) or not to receive (n ϭ 15) CMV hyperprophylaxis of CMV infection or disease in seronegative immune globulin. Patient characteristics are shown in Table allogeneic bone marrow transplant recipients from a 1. The pretransplant conditioning and GVHD prophylaxis seropositive donor.were given according to routine practice at each centre. Keywords: cytomegalovirus hyperimmune globulin; More than half of the patients received low-dose acyclovir cytomegalovirus infection; allogeneic bone marrow transfor herpes simplex virus prophylaxis, but no other prophyplantation lactic antiviral agent was permitted. The immunoglob...