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Both European Group for blood and marrow transplantation risk score (EBMT score modified model) and hematopoietic cell transplantation comorbidity index (HCT-CI) are suitable for evaluating patients undergoing unmanipulated haploidentical blood and marrow transplantation (HBMT), while the predictive capacity of the combined model following haploidentical transplantation is still unknown. In this study, we calculated and validated 322 consecutive unmanipulated HBMT patients. Patients in groups with HCT-CI scores of 0 or 1-2 exhibited similar overall survival (OS), non-relapse mortality (NRM), and relapse rates, independent of their EBMT score modified model. In the group in which patients' HCT-CI scores were ≥3, patients with high EBMT score modified model showed lower OS (p = 0.003) and higher NRM (p = 0.001) than did patients with low EBMT score. In conclusion, this combined model can be used to predict outcomes and may improve the stratification of high-risk patients following unmanipulated HBMT.

This retrospective study compared the transplantation outcomes of 98 consecutive patients with acute leukemia. Allogeneic hematopoietic stem cell transplantation was performed using G-CSF-mobilized bone marrow and blood (G-BM&PB) or G-CSF-mobilized peripheral blood (G-PB) from HLA-identical sibling donors. The G-BM&PB and G-PB groups displayed significantly different neutrophil recovery rates (medians of 15 vs. 14 d, respectively; p = 0.009) but similar platelet recovery rates. The cumulative incidences of grades II-IV acute graft-versus-host disease (aGVHD) in the G-BM&PB and G-PB cohorts were similar (16.2 ± 4.7% vs. 21.8 ± 7.4%, respectively; p = 0.676), but the incidences of grades III-IV aGVHD were significantly different (5.5 ± 3.1% vs. 18.9 ± 7.1%, respectively; p = 0.042). The G-BM&PB and G-PB cohorts displayed similar cumulative incidences of chronic GVHD (cGVHD, 49.1 ± 5.7% vs. 42.7 ± 6.8%, respectively; p = 0.465), one-yr cumulative incidences of treatment-related mortality (16.5 ± 3.5% vs. 24.4 ± 4.1%, respectively; p = 0.220), and five-yr cumulative incidences of relapse (13.9 ± 4.8% vs. 26.8 ± 7.2%, respectively; p = 0.113). The five-yr probability of leukemia-free survival (LFS) was significantly higher in the G-BM&PB group than in the G-PB group (77.8 ± 5.2% vs. 57.6 ± 8.6%, respectively; p = 0.023). Multivariate analysis identified G-PB as an independent risk factor for grades III-IV aGVHD and LFS. Our results suggest that HLA-identical transplantation with G-BM&PB results in superior clinical outcomes compared with G-PB for patients with acute leukemia., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Either WT1 or leukemia-associated aberrant immune phenotypes (LAIPs) was one of the minimal residual disease (MRD) parameters used to predict leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We first evaluated the clinical value of various positive MRD standards for accurately indicating relapse based on WT1 and FCM data in adult patients with acute leukemia (AL). In total, 824 AL patients treated with allo-HSCT were enrolled in this study. We compared the sensitivity and specificity of diverse, multiple-criteria MRD prognostic standards based on WT1 and FCM assays. Higher sensitivity was achieved without a loss of specificity when MRDco+, which was defined as two consecutive WT10.6+ or FCM+ or both WT10.6+ and FCM+ in the same sample within a year posttransplantation, was used as the positive MRD standard. Similar results were observed, even in 484 patients who had both abnormal WT1 and LAIPs values before transplant. A multivariate analysis showed that MRDco+ was an independent risk factor for leukemia relapse after transplant in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The combined use of FCM and WT1 monitoring could distinguish between patients with low and high risks of relapse. Various positive MRD standards were useful for guiding intervention.

Background: Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival (LFS) and some primary results, such as hematologic recovery, risk of graft-versus-host disease (GVHD), relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source., Methods: The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood (UCBT) as a primary unrelated stem cell source (n = 38), bone marrow (UBMT n = 28, transplanted before January 2003), or peripheral blood stem cells (UPBSCT n = 46, transplanted after January 2003) between July 2000 and July 2008 were analyzed., Results: Except that the patients were much younger in the UCBT group (median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT), other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti-thymocyte globulin (ATG) used for the UBMT patients (2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P = 0.000). Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower (87.8% vs. 97.8% vs. 100% for WBC, P = 0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P = 0.000) for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease (aGVHD) was much higher in the UBMT group but did not differ among the other groups (51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P = 0.000). The occurrence of extensive chronic GVHD (cGVHD) was significantly decreased for recipients of UCBT (4%) compared with that of UPBSCT (39.1%) and UBMT (49.1%, P = 0.000), although the rates of whole cGVHD were not significantly different (30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively). The patients had a similar rate of CMV infection (21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively), while the HC occurrence was lower after UCBT (7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively). As of August 2012, there was no apparent difference in 5-year overall survival (OS), LFS, or the relapse rate for each graft source (52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT)., Conclusion: These data support the use of UCB donors as an alternative allogeneic donor.

A total of 123 consecutive patients with advanced-stage, acute leukemia undergoing HSCT from HLA-identical sibling donors were analyzed. A G-CSF-primed DLI was planned within day 60 post-transplantation before hematologic relapse was diagnosed. Fifty of the 123 individuals received prophylactic DLI, and 73 individuals received no prophylactic treatment. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was 17% for patients receiving DLI and 23% for patients not receiving DLI (p = 0.35). The incidence of chronic GVHD was 38% for patients receiving DLI and 17% for patients not receiving DLI (p = 0.021). The two-yr cumulative incidence of relapse was significantly lower in patients who received prophylactic DLI (46%) compared with patients who did not receive prophylactic DLI (66%) (p = 0.02). The three-yr probability of overall survival was higher in patients who received prophylactic DLI (36%) than in patients who did not receive prophylactic DLI (11%) (p = 0.001). The leukemia-free survival was also higher in patients who received prophylactic DLI (29%) than in patients who did not receive prophylactic DLI (9%) (p = 0.001). Our comparisons suggest that the prophylactic use of DLI can significantly increase survival of patients with advanced-stage, acute leukemia who receive HLA-identical sibling HSCT., (© 2012 John Wiley & Sons A/S.)

The relative importance of various human leukocyte antigen (HLA) loci has not been established for unmanipulated HLA-mismatched/haploidentical transplantation. To address this question, we analyzed the impact of HLA-A, HLA-B, HLA-DRB1, HLA-DRB3, HLA-DRB4, and HLA-DRB5 on the outcome of HLA-haploidentical transplantation. Four hundred and eighty-one donor-recipient pairs were fully typed before transplantation. In univariate analysis, HLA-B mismatch not only demonstrated significant adverse effects on acute graft-versus-host disease (GVHD) and transplant-related mortality but also was associated with reduced overall survival and leukemia-free survival (LFS). In multivariate analysis, HLA-B mismatch remained the independent risk factor for acute GVHD and transplant-related mortality. The high risk of disease and the female donor were found to be significant factors for reduced overall survival and LFS. Furthermore, multiple mismatch of the HLA locus was found to have no synergistic adverse effect on outcomes. Our results suggest that prospective matching of patients and donors for HLA-B antigen in the unshared HLA haplotype is warranted for HLA-mismatched/haploidentical transplantation., (© 2011 John Wiley & Sons A/S.)

Currently, limited information is available regarding the effects of early lymphocyte recovery on transplant outcomes in pediatric patients with hematological malignancies after unmanipulated haploidentical transplantation. In this study, we evaluated the association of Day 30 absolute lymphocyte count (ALC-30) with transplant outcomes in 60 consecutive pediatric patients with hematological malignancies receiving T-cell-repleted transplantation from an haploidentical related donors. After median follow-up of 36 months (range, 1.4-75 months), higher relapse rate was observed in patients with an ALC-30 < 300 cells/μL compared to patients with an ALC-30 ≥ 300 cells/μL (35.5% vs. 13.8%, P = 0.049). More patients died of infections in those with an ALC-30 < 300 cells/μL compared with patients with an ALC-30 ≥ 300 cells/μL (25.8% vs. 3.4%, P = 0.015). The ALC-30 above the cutoff value 300 cells/μL was associated with improved overall-survival (HR 0.301, 95% CI 0.117-0.771; P = 0.012), leukemia free survival (HR 0.195, 95% CI 0.078-0.498; P=0.002), less relapse (HR 0.224 95% CI 0.070-0.717; P = 0.012), and less transplant- related mortality (HR=0.166; 95%CI 0.037-0.750; P = 0.020). Our results suggest that a higher ALC-30 ≥ 300 cells/μL) could be a useful and simple tool to predict pediatric patients with a superior outcome after unmanipulated haploidentical transplantation.

Objective: To investigate the characteristics of liver enzyme between acute graft-versus-host disease (aGVHD) and non-aGVHD groups after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: The liver enzyme data of patients with or without aGVHD was analyzed., Results: Among the 371 patients, 158 developed aGVHD (41.6%) with a median time of 29.5 d. In non-aGVHD group, the median elevating times of ALT, AST, GGT, LDH were all ≤ 20 d after transplantation, which were significantly earlier than those of aGVHD group. The peak value of AST was much higher in aGVHD group, but the remaining liver enzyme showed no significant difference. In aGVHD group, the duration of AST, GGT and LDH was significantly longer than the non-occurrence of aGVHD group, but ALT and ALP showed no difference in duration. In ALT, AST, ALP and LDH elevating group, the occurrence rate of aGVHD was significantly higher, but only ALT and LDH elevation could enter logistic regression model. The sensitivity and veracity of ALT or LDH elevating only were not very good for the diagnosis of aGVHD, but if ALT and LDH both elevated after day 24 and persisted more than 22 d, the sensitivity and veracity were better., Conclusions: The change of liver enzyme is common in allo-HSCT and associates with the occurrence of aGVHD, and the liver enzyme elevating only may not be a good diagnostic index of aGVHD. If the dynamic characteristics of liver enzyme is taken into account and the effect of drug-induced liver injury could be excluded, the elevation of liver enzyme still have the diagnostic value of aGVHD.

Objective: Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplant strategy for pediatric patients with hematological diseases. The aim of this study was to investigate the effects of donor and recipient characteristics on hematopoietic recovery in pediatric patients following unmanipulated haploidentical transplantation., Methods: Factors correlating with hematopoietic recovery in 133 pediatric patients after unmanipulated haploidentical transplantation were analyzed retrospectively., Results: All patients reached an absolute neutrophil count of 500/microl in a median of 12 days (range, 9-49 days). One hundred thirty-three patients reached an untransfused platelet count of more than 20,000/microl in a median of 15 days (range, 7-180 days). Univariate analysis showed five factors associated with platelet engraftment. These were time to transplantation after diagnosis (P = 0.072), infused nuclear cells/kg of recipient weight (P = 0.028), CD3+ cells/kg of recipient weight (P = 0.082), CD4+ cells/kg of recipient weight (P = 0.083), and CD34+ cells/kg of recipient weight (P = 0.012). Multivariate analysis showed that infused CD34+ cells/kg of recipient weight (CD34+ cells more than 2.42 x 10(6)/kg vs. less than or equal to 2.42 x 10(6)/kg, HR = 1.733; 95% CI 1.222-2.549; P = 0.002) were significantly associated with an increased risk of platelet engraftment. Patients receiving a CD34+ cell dose more than 2.42 x 10(6)/kg had a short time [12 days (range, 7-176 days)] to achieve an untransfused platelet engraftment, compared to 18 days (range, 7-180 days) in patients receiving a lower dose (P < 0.001)., Conclusions: Our results suggest that low number of CD34+ cells in allografts is a critical factor associated with delayed platelet engraftment after unmanipulated haploidentical transplantation in pediatric patients.

Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplantation strategy for patients without an HLA-matched related or unrelated donor. In this transplantation setting, factors associated with hematopoietic recovery have not been defined completely. The aim of this study was to investigate the effects of donor and recipient characteristics on neutrophil and platelet engraftment after unmanipulated HSCT. The study group comprised 348 patients who underwent unmanipulated haploidentical blood and marrow transplantation to treat hematologic malignancy at a single institution between 2002 and 2007. Factors correlating with neutrophil and platelet engraftment posttransplantation were analyzed retrospectively. All patients achieved an absolute neutrophil count ANC of 500/microL in a median of 13 days (range, 9 to 49 days). Of the 348 patients, 331 (95.11%) achieved an untransfused platelet count of > 20,000/microL in a median of 16 days (range, 7 to 356 days). Multivariate analysis showed that the amount of CD34(+) cells infused (CD34(+) cells >or= 2.19 x 10(6)/kg recipient weight vs < 2.19 x10(6)/kg recipient weight; hazard ratio [HR] = 1.695; 95% confidence interval [CI] = 1.361 to 2.112; P < .0001), and disease stage (advanced vs early; HR = 0.724; 95% CI = 0.577 to 0.907; P = .005) were independently associated with increased risk of platelet engraftment. Our results suggest that low numbers of CD34(+) cells in allografts and advanced-stage disease may be critical factors associated with delayed platelet engraftment after unmanipulated haploidentical transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the best therapeutic options to cure acute leukemia (AL). However, many patients have no human leukocyte antigen (HLA)-matched donor. Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion (TCD). This method combined granulocyte-colony stimulating factor (G-CSF)-primed bone marrow and peripheral blood with intensive immunosuppression. We analyzed the outcome of 250 consecutive patients with AL who underwent HLA-mismatched/haploidentical transplantation with 1-3 mismatched loci of HLA-A, B, and DR from family donors via our new transplant protocol. Two hundred forty-nine patients achieved sustained, full donor chimerism. The incidence of grade 2-4 acute graft-versus-host disease (aGVHD) was 45.8%, and that of grades 3 and 4 was 13.4%, which was not associated with the extent of HLA disparity. The cumulative incidence of total chronic GVHD (cGVHD) was 53.9% and that of extensive cGVHD was 22.6% in 217 evaluable patients. One hundred forty-one of the 250 patients survived free of disease recurrence at a median of 1092 days (range: 442-2437 days) of follow-up. Seventeen patients received DLI as a treatment for relapse after transplantation and 7 patients achieved leukemia-free survival (LFS). The 3-year probability of LFS for acute myelogenous leukemia (AML) was 70.7% and 55.9%, and for acute lymphoblastic leukemia (ALL) it was 59.7% and 24.8% in standard-risk and high-risk groups, respectively. Lower LFS were associated with diagnosis of acute leukemia in the high-risk group (P= .001, relative risk [RR], 95% confidence interval [CI]: 2.94[1.535-5.631]) and the occurrence of aGVHD of grades 3 and 4 (P= .004). HLA-mismatched/haploidentical HSCT was feasible with unmanipulated blood and bone marrow harvest.

Objectives: The goal of this study was to explore the role of NK cell alloreaction in predicting prognosis under unmanipulated HLA-haploidentical blood and marrow transplantation and examine whether the presence of any individual donor-activating KIR gene had an influence on the clinical outcome., Methods: We studied the HLA and KIR genotype of 64 donor-recipient pairs, who underwent transplantation., Results: In contrast to Perugia's KIR ligand-ligand mismatch model or Handgretinger's KIR receptor-ligand mismatch model or Bignon's KIR gene-gene mismatch model between donor-recipient pairs, we found that the cumulative incidence of 3-yr disease-free survival (DFS), overall survival (OS), and transplantation-related mortality (TRM) were best predicted by the number of KIR ligands carried by patients (HR 0.355, 95% CI 0.186-0.678, P = 0.002 for DFS; HR 0.445, 95% CI 0.233-0.848, P = 0.014 for OS; HR 0.450, 95% CI 0.219-0.926, P = 0.030 for TRM). Moreover, an analysis of KIR ligand numbers was found to be correlative in patients with lymphoid malignancy. The KIR ligand-ligand mismatch model is a good predictor of acute graft vs. host disease (aGVHD; HR 3.812, 95% CI 1.667-8.720, P = 0.002). Meanwhile, the presence of donor-activating KIR2DS3 also contributed significantly to acute (HR 2.967, 95% CI 1.265-6.958, P = 0.012) and chronic GVHD (HR 2.541, 95% CI 1.127-5.730, P = 0.025)., Conclusions: These data indicate that prognosis after transplantation is associated with the numbers of KIR ligands in recipients and T-cell alloreaction may play a predominant role in this model.

Objective: To compare the outcomes in hematological patients receiving unrelated peripheral blood stem cell transplants (UPBSCT) with those receiving unrelated bone marrow transplants (UBMT) in a retrospective analysis., Methods: Sixty-three patients with hematological diseases with HLA-matched (65%) or mismatched (35%) unrelated donors were receiving UPBSCT (n = 33) or UBMT (n = 30) between May 2001 and June 2005 in our institute. They all received standard conditioning regimens with Bu/Cy (n = 53) or TBI/Cy (n = 10) with the addition of ATG for 3 - 4 days (n = 58) or CD3 antibody (n = 5). There were more patients receiving rabbit ATG in the UPBSCT group than UBMT (21/33 vs 8/25, P = 0.02) and the remaining patients received pig ATG. Graft versus host disease (GVHD) prophylaxis consisting of cyclosporine, methotrexate and mycophenolate mofetil were the same., Results: The two groups were matched for the following factors: gender, diagnosis, HLA-compatibility and conditioning regimens. The median age in the UPBSCT group was 29.5 (10 - 47) years and in the UBMT 21.5 (7 - 42) years (P < 0.05). The UPBSCT group consisted of 10 females and 23 males and the UBMT group 7 females and 23 males. Eleven patients in the UPBSCT and 8 patients in the UBMT group were diagnosed with as chronic myeloid leukemia (CML); 9 and 12 as acute myelocytic leukemia (AML); 11 and 10 as acute lymphatic leukemia (ALL); 2 and 0 as severe aplastic anemia (SAA). There were more patients in aggressive stage (>CR1) in the UBMT group than in the UPBSCT group (9/30 vs 3/33, P = 0.06). Median follow-up was 12 months after UPBSCT and 20 months after UBMT (P < 0.05). UPBSCT group had a higher number of infused MNC as comparison with UBMT group (6.16 x 10(8)/kg vs 2.80 x 10(8)/kg, P < 0.05). Both neutrophil and platelet recovery were faster after UPBSCT (11 days vs 17 days, 14 days vs 27.5 days, P < 0.01). Although the cumulative incidence of grades II - IV acute GVHD and severe aGVHD in the UPBSCT group were less than in the UBMT group (33.04% vs 66.69%, 7.26% vs 34.52%, P < 0.05), there was no difference after the source of ATG was counted. The incidence of chronic GVHD did not differ between the two groups (18/25 vs 14/22). Relapse including molecular relapse occurred in 6 of the 31 patients after UPBSCT and in 4 of the 30 patients after UBMT (P > 0.05). Finally, fifteen of the 30 patients died after UBMT, as compared with 8 of the 33 patients after UPBSCT. The cumulative overall survival was 62.45% after UPBSCT and 47.22% after UBMT (P = 0.114)., Conclusion: Our results indicate that UPBSCT led to significantly faster leukocyte and platelet engraftment without increasing the incidence of aGVHD and the overall survival was comparable between the two methods of therapy.

The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n = 158) or related HLA-mismatched (n = 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 + ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P = .13), respectively, with the relative risk (RR) = 0.64 (95% CI, 0.43-0.94), P = .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P = .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P = .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P = .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P = .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P = .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes.

Objective: To explore the clinical application of human leukocyte antigen (HLA) mismatched hematopoietic stem cell transplantation (HSCT) for malignant hematological diseases using a new GIAC protocol., Methods: One hundred patients with malignant hematological disease received G-CSF mobilization, intensive immunosuppression, ATG and combination of bone marrow and peripheral blood stem cell transplantation at least 1 locus mis-matched hematopoietic stem cell transplant performed with GIAC protocol. The conditioning regimen was intensified and prolonged with combined use of CsA, MMF and ATG for GVHD prophylaxis., Results: All patients achieved sustained, full donor-type engraftment. The cumulative incidence of grade II approximately IV aGVHD was 48.39%, and grade III approximately IV aGVHD was 12.90%. Thirty-eight patients had cGVHDs which were of extensive type in 11 patients. Twelve patients relapsed, 11 of them were high-risk patients, and 3 returned to CR after donor lymphocyte infusion. Twenty-two patients died, owing to recurrent diseases in 6 and transplant-related complications in 16 cases. Seventy-two patients were alive and disease free, with 1 year disease-free survival probabilities for standard and high risk patients of (83.52 +/- 7.41)% and (47.63 +/- 8.49)%, respectively., Conclusion: The GIAC protocol for at least 1 locus mismatched hematopoietic stem cell transplantation is relatively safe and efficient for patients with hematological malignancies.

We investigated whether early lymphocyte recovery, after unmanipulated, haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in 78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC-30). Patients with high ALC-30 (≥ 300 cells/μL) had lower relapse rates (13.8% vs. 35.5%, p = 0.049) and lower incidence of bacterial infections (3.4% vs. 25.8%, p = 0.015) than those with low ALC-30 values. Multivariate analysis showed that a high ALC-30 was associated with improved overall survival (OS, hazard ratio [HR]: 0.099, 95% confidence interval [CI]: 0.029-0.337; p < 0.0001), improved leukemia-free survival (HR: 0.245, 95% CI: 0.112-0.539; p < 0.0001), lower relapse rate (HR: 0.096, 95% CI: 0.011-0.827; p = 0.033) and lower transplant-related mortality (TRM, HR: 0.073, 95% CI: 0.016-0.324; p = 0.001). Combinations of three mismatches in the human leukocyte antigen loci were associated with a higher TRM (HR: 5.026, 95% CI: 1.392-18.173; p = 0.014). Our results suggest that the ALC-30 can predict a favorable OS after unmanipulated HBMT. [ABSTRACT FROM AUTHOR]

Abstract: Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplantation strategy for patients without an HLA-matched related or unrelated donor. In this transplantation setting, factors associated with hematopoietic recovery have not been defined completely. The aim of this study was to investigate the effects of donor and recipient characteristics on neutrophil and platelet engraftment after unmanipulated HSCT. The study group comprised 348 patients who underwent unmanipulated haploidentical blood and marrow transplantation to treat hematologic malignancy at a single institution between 2002 and 2007. Factors correlating with neutrophil and platelet engraftment posttransplantation were analyzed retrospectively. All patients achieved an absolute neutrophil count ANC of 500/μL in a median of 13 days (range, 9 to 49 days). Of the 348 patients, 331 (95.11%) achieved an untransfused platelet count of > 20,000/μL in a median of 16 days (range, 7 to 356 days). Multivariate analysis showed that the amount of CD34+ cells infused (CD34+ cells ≥ 2.19 × 106/kg recipient weight vs < 2.19 ×106/kg recipient weight; hazard ratio [HR] = 1.695; 95% confidence interval [CI] = 1.361 to 2.112; P < .0001), and disease stage (advanced vs early; HR = 0.724; 95% CI = 0.577 to 0.907; P = .005) were independently associated with increased risk of platelet engraftment. Our results suggest that low numbers of CD34+ cells in allografts and advanced-stage disease may be critical factors associated with delayed platelet engraftment after unmanipulated haploidentical transplantation. [Copyright &y& Elsevier]

Abstract: The effect of natural killer (NK) cell alloreactivity on the outcome of haploidentical hematopoietic stem cell transplantation (HSCT), with or without in vitro T cell depletion, remains controversial. Killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen C and B epitopes on target cells, thereby regulating NK cell activity. To examine the recovery of CD94:NKG2A and KIR (CD158a, CD158b, and CD158e) expression by NK cells, we used flow cytometry to evaluate samples from 24 patients and their donors before and in the year following unmanipulated HLA-haploidentical/mismatched blood and marrow transplantation. Linear regression analysis demonstrated that NKG2A recovery was inversely correlated with CD158b recovery in the year following transplant. The doses of T cell subgroups CD4+ and CD8+ were inversely associated with CD158a and CD158e expression during the 2 months following transplantation. Moreover, patients with grades II-IV acute graft-versus-host disease (aGVHD) or who received “high” doses of T cells (>1.37 × 108/kg) showed delayed recovery of KIRs during the 2 months following transplantation. Univariate analysis showed that patients with high CD94 expression by day 60 (>90%) or who received donors with high CD94 expression (>80%) were associated with higher transplantation-related mortality (P = .006 or .067, respectively) and poorer leukemia-free survival (P = .012 or .094, respectively). Thus, the occurrence of aGVHD or the receipt of high doses of T cells in the allograft altered KIR reconstitution. Furthermore, high levels of CD94 expression in donors or in recipients by day 60 might be a good predictor for poor prognosis. [Copyright &y& Elsevier]