Unrelated Bone Marrow Transplantation Research Articles

Successful unrelated bone marrow transplantation for a human immunodeficiency virus type-1-seropositive acute myelogenous leukemia patient following HAART

The availability of highly active anti-retroviral therapy (HAART) has greatly improved the outcome of human immunodeficiency virus type-1 (HIV-1) infection and disease. We report here on a case of an HIV-1-seropositive patient with acute myelogenous leukemia who underwent a successful allogeneic unrelated bone marrow transplantation following HAART. A 40-year-old Japanese HIV-seropositive man underwent allogeneic unrelated bone marrow transplantation using a myeloablative pretransplant-conditioning regimen. Neutrophil engraftment occurred on day +18, and donor chimerism was achieved on day +27. During pre- and post- transplantation, the HAART was not interrupted. Over 1 year after transplantation, the patient is alive and in continuous complete remission with undetectable levels of HIV-1 RNA. HAART can lead to a successful hematopoietic stem cell transplantation without severe opportunistic infections.

Unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients: A meta-analysis

The effect of unrelated donor bone marrow transplantation (UBMT) and unrelated donor cord blood transplantation (UCBT) on the outcome of patients with hematological diseases remains controversial. We conducted a meta-analysis using data from controlled clinical trials comparing UCBT to UBMT in patients undergoing hematopoietic stem cell transplantation. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of chronic graft-versus-host disease (GVHD) was lower with UCBT (relative risk [RR] = 0.41; 95% confidence interval [CI] (0.25, 0.68)), and the incidence of grades II–IV aGVHD was also significantly different (RR = 0.69; 95% CI (0.55, 0.86)). The incidence of relapse was also lower with UCBT (RR = 0.72; 95% CI (0.59, 0.87)). There was no difference in OS in children when studies were pooled (Hazard ratio [HR] = 1.25; 95% CI (0.87, 1.78)). For adults, OS (HR = 1.26; 95% CI (1.13, 1.40)) was statistically different. Thus, UCBT led to inferior outcomes than UBMT in adults.

Prediction of nucleated cells in bone marrow stem cell products by donor characteristics: a retrospective single centre analysis

Number of total nucleated cells is an important prognostic factor of unrelated bone marrow transplantation. The objective of our study was to further optimize donor selection by finding donor characteristics which predict the total nucleated cell concentration in unrelated bone marrow products. Data were collected retrospectively from the pre-donation medical records. The outcome variable was concentration of total nucleated cells in the final products. We investigated several candidate predictors, including demographic variables and peripheral blood counts. A backward selection procedure was performed, using multivariable multilevel analysis. A total of 471 donations were included. Significant predictors were increase of age (ratio per 5 years 0.971), cytomegalovirus (ratio 0.947 if positive), smoking (ratio 1.079 if yes), higher haemoglobin (ratio 1.052 per mmol/l), higher mono-nuclear cells (ratio 1.169 when mono-nuclear cells >2.69 compared to mono-nuclear cells <1.89 x 10E9/l), increasing number of whole blood donations (ratio 1.115 when blood donations >4 compared to blood donation <1), and larger body surface area (ratio 1.179 when body surface area >2.07 compared to body surface area <1.82 m(2)). The model was adjusted for collection volume. Presence of all favourable factors was associated with a twofold higher concentration of total nucleated cells in the bone marrow harvest.

Significant Impact of IL-17A Gene Polymorphism On Transplant Outcomes After HLA-Fully-Matched Unrelated Bone Marrow Transplantation.

Abstract 2305Poster Board II-282IL-17 plays an active role in autoimmune diseases and organ transplant rejection through its mediating proinflammatory responses and inducing inflammatory cytokine and chemokine production. This study examined the impact of donor and recipient polymorphism in the IL-17A gene on the clinical outcomes in unrelated HLA-fully-matched myeloablative bone marrow transplantation (BMT) through the Japan Marrow Donor Program. The IL-17A polymorphism (rs2275913, G197A) was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. In patients with standard risk disease, the donor IL-17A-197A genotype was associated with significantly improved OS (adjusted HR, 0.32; 95% CI, 0.13-0.79; p=0.01) and reduced transplant related mortality (TRM) (adjusted HR, 0.27; 95% CI, 0.11-0.67; p=0.005), but no impact on disease relapse or the development of grades II-IV acute GVHD or chronic GVHD. Patients with standard risk disease receiving transplants from donors with the 197A genotype had better 5-year OS (71% vs. 40%, p=0.02; Figure) and lower 5-year TRM rate (27% vs. 60%, p=0.02). The IL-17A polymorphism did not significantly influence the transplant outcomes in patients with high risk disease. These results suggest transplantation from IL-17A-197A positive donor is advantageous in improving OS and reducing TRM after HLA-matched unrelated BMT for standard risk hematologic malignancies. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Pretransplant Conditioning with Campath-1H (Alemtuzumab) in Pediatric Matched Unrelated Bone Marrow Transplants - An Institutional Experience.

Abstract 4651 IntroductionGraft versus host disease remains a major cause of mortality and morbidity following matched unrelated hematopoietic stem cell transplantation. Campath-1H (Alemtuzumab) is a humanized monoclonal antibody to CD52, an antigen expressed on T and B lymphocytes, monocytes and natural killer cells and is thought to reduce GVHD incidence through in vivo T cell depletion. Through the same mechanism it can potentially increase the risk of relapse by reducing the graft vs. leukemia effect and also possibly increase the risk of infection due to delayed immune recovery. This study looks at our experience with Campath-1H substituted in place of the conventional anti-thymocyte globulin (ATG) in our transplant conditioning regimen. Patients and MethodsThis retrospective case study included 17 pediatric (9 male; 8 female) matched unrelated bone marrow transplants done in our institution between January 2003 and June 2009 with Campath-1H as part of the pretransplant conditioning regimen. The primary transplant indication was leukemia/lymphoma (n=9), MDS/ MDS evolving into AML (n= 3), severe aplastic anemia (n=4) and Fanconi anemia (n=1). The conditioning regimen included Campath-1H given with cytoxan/ total body irradiation (TBI) in 14 patients, fludarabine/ TBI in 2 patients, and melphalan/ fludarabine in 1 patient. Campath-1H dosing was body weight based: 3mg (if between 5-15kg), 5 mg (if between 16-30kg) and 10 mg (if >30 kg) and 3 doses were administered when underlying condition was a malignancy and 4 doses when it was a bone marrow failure state. The last dose was given at least 24 hours prior to the bone marrow/ peripheral stem cell infusion. GVHD prophylaxis was with tacrolimus/methotrexate (n=12), tacrolimus (n=4) and cyclosporine/methotrexate (n=1). Standard institutional infectious prophylaxis was followed. ResultsThe median age at transplant was 12.2 years (range; 0.7-19.7 years). All but one patient engrafted with a median of 21 days (range; 14-25 days). 5 out of 17 developed Grade I-II acute GVHD which resolved with steroids. No patient developed chronic GVHD. One patient had a CMV reactivation but no patient developed active CMV disease. 4 patients had varicella one of whom died of disseminated infection (day +376). The same patient also had adeno viral infection and BK viremia. 1 patient developed PCP pneumonia and retinal toxoplasmosis. 5 patients (6 transplants) relapsed (range; 40-641 days) with 3 relapsing within +100 days. 1 patient developed PTLD which was successfully treated with rituximab. Of the 4 patient deaths 3 were due to relapse and one due to disseminated varicella infection. The median follow-up time was 719 days (range; 147-2175 days). Overall survival as calculated using the Kaplan-Meir analysis was 100 % at 100 days and 94% at 1 year. Event free survival censoring for death, relapse and rejection was 76% at 100 days and 64% at 1 year. ConclusionsBased on our experience, Campath-1H used as part of pretransplant conditioning regimen in pediatric matched unrelated transplants seems to reduce the risk of serious GVHD. This is in concordance with other published literature. T cell depletion is considered to increase the risk of life threatening infections. Our study had one infection related death. There were no patients with active CMV disease. This may in part be attributed to strict prophylactic measures and increased surveillance. Longer duration of follow-up is required to adequately analyze the relapse rates. Also, given our small patient numbers the effect of primary disease state and stage on relapse could not be assessed. Larger studies in the pediatric population with longer duration of follow-up comparing Campath-1H with conventional regimens are required to further assess its role with regards to graft vs. leukemia effect and also to establish if the decreased incidence of GVHD is sustained in larger cohorts. Disclosures:No relevant conflicts of interest to declare.

Growth Velocity in Pediatric Bone Marrow Transplantation: Significance of Donor Type and Treatment Factors

Children who have undergone bone marrow transplantation (BMT) often have decreased growth. Growth is a multifactorial process, and the factors that influence growth after BMT are not completely understood. The authors hypothesized that donor type may be a factor influencing growth. Sixty-five children and adolescents who underwent BMT (32 related matched, 33 unrelated matched) were evaluated. Growth velocity (height standard deviation) was assessed prior to and 2 years following BMT. The results indicated that children and adolescents who underwent unrelated matched transplants had lower growth velocity (P < .059) than those with related matched transplants. Those who received the standard conditioning regimen that included total body irradiation (TBI) had a significantly lower growth velocity (P < .045) than those with chemotherapy-only regimens. Significant correlates of growth velocity included younger age at BMT and pre-BMT growth velocity. Thus, donor type, age at BMT, prior treatment, and BMT conditioning regimens that include TBI may all affect growth post-BMT. Careful monitoring of growth velocity is required for patients who have received an unrelated donor BMT.

Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis in Japan

Post-transplant outcomes of hemophagocytic lymphohistiocytosis (HLH) patients were analyzed in Japan where Epstein-Barr virus (EBV)-associated severe forms are problematic. Fifty-seven patients (43 familial HLH [12 FHL2, 11 FHL3, 20 undefined], 14 EBV-HLH) who underwent stem cell transplantation (SCT) between 1995 and 2005 were enrolled based on the nationwide registration. Fifty-seven patients underwent 61 SCTs, including 4 consecutive SCTs. SCTs were employed using allogeneic donors in 93% of cases (allo 53, twin 1, auto 3). Unrelated donor cord blood transplantation (UCBT) was employed in half of cases (21 FHL, 7 EBV-HLH). Reduced intensity conditioning was used in 26% of cases. The 10-year overall survival rates (median +/- SE%) were 65.0 +/- 7.9% in FHL and 85.7 +/- 9.4% in EBV-HLH patients, respectively. The survival of UCBT recipients was >65% in both FHL and EBV-HLH patients. Three out of four patients were alive with successful engraftment after second UCBT. FHL patients showed a poorer outcome due to early treatment-related deaths (<100 days, seven patients) and a higher incidence of sequelae than EBV-HLH patients (P = 0.02). The risk of death for FHL patients having received an unrelated donor bone marrow transplant was marginally higher than that for a related donor SCT (P = 0.05) and that for UCBT (P = 0.07). EBV-HLH patients had a better prognosis after SCT than FHL patients. FHL patients showed either an equal or better outcome even after UCBT compared with the recent reports. UCB might therefore be acceptable as an alternate SCT source for HLH patients, although the optimal conditioning remains to be determined.

Tacrolimus/Methotrexate versus Cyclosporine/Methotrexate as Graft-versus-Host Disease Prophylaxis in Patients with Severe Aplastic Anemia Who Received Bone Marrow Transplantation from Unrelated Donors: Results of Matched Pair Analysis

Tacrolimus (FK) and cyclosporine (CsA) have been shown to be effective in the prophylaxis of graft-versus-host disease (GVHD). However, no comparative studies have yet been conducted to examine the efficacy of FK/methotrexate (MTX) and CsA/MTX in patients with severe aplastic anemia (SAA) given unrelated donor bone marrow transplantation (U-BMT). We used matched-pair analysis to compare FK/MTX with CsA/MTX in patients with SAA who received U-BMT through the Japan Marrow Donor Program. Forty-seven pairs could be matched exactly for recipient age and conditioning regimens. Forty-five patients achieved engraftment in the FK group and 42 patients in the CsA group. The probability of grade II-IV acute GVHD (aGVHD) was 28.9% in the FK group and 32.6% in the CsA group (P=.558). The probability of chronic GVHD (cGVHD) was 13.3% in the FK group and 36.0% in the CsA group (P=.104). The 5-year survival rate was 82.8% in the FK group and 49.5% in the CsA group (P=.012). The study shows the superiority of FK/MTX over CsA/MTX in overall survival because of the lower incidence of transplantation-related deaths. A prospective randomized study comparing FK/MTX and CsA/MTX is warranted.

Primary central nervous system post‐transplant lymphoproliferative disorder presenting as cerebral hemorrhage after unrelated bone marrow transplantation

We present a rare case of cerebral hemorrhage due to Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD). A 58-year-old man with myelodysplastic syndrome received allogeneic hematopoietic stem cell transplantation from an unrelated donor after being conditioned with fludarabine, melphalan, and total body irradiation. Tacrolimus and methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. On day 23, he developed acute GVHD, which was successfully treated with prednisolone (PSL). The tapering of PSL failed because of extensive chronic GVHD involving the liver and lungs, and mycophenolate mofetil was added on day 244. On day 340, the patient suddenly complained of severe headache. Computed tomography confirmed subcortical hemorrhage, and he died on day 348. The autopsy revealed atypical lymphocytes infiltrating the brain and meninges, which were positive for B-cell-associated antigens and EBV-encoded RNA, and thus EBV-associated PTLD was diagnosed.

Ten years of cord blood transplantation: from bench to bedside

Cord blood is an unlimited source of haematopoietic stem cells for allogeneic haematopoietic stem cell transplant. Since the first human cord blood transplant, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic haematopoietic stem cell transplant. More than 400 000 cord blood units are now available for international exchange. Results of unrelated allogeneic cord blood transplants in malignant and non-malignant diseases, in adults and children, show that, compared to human leucocyte antigen (HLA)-matched unrelated bone marrow transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of graft-versus-host disease and better long-term immune recovery resulting in a similar long term survival. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. Progress is expected to facilitate engraftment and reduce transplant-related mortality and includes reduced intensity conditioning regimen, intra bone injection of cord blood cells and double cord blood transplants. In addition to haematopoietic stem cells, cord blood and placenta contain a high number of non-haematopoietic stem cells that explains the increasing interest of using cord blood for developing regenerative medicine.

Outcome of 125 Children with Chronic Myelogenous Leukemia Who Received Transplants from Unrelated Donors: The Japan Marrow Donor Program

Because of a small number of patients, only a few studies have addressed the outcome of bone marrow transplantation (BMT) in children with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), who receive graft from a volunteer-unrelated donor (VUD), especially after practical application of imatinib mesylate. The outcomes of BMT from a VUD in 125 children with Ph+ CML were retrospectively reviewed. Patients were identified through the Japan Marrow Donor Program as having undergone BMT between 1993 and 2005 and were aged 1-19 years at the time of transplant (median age, 14 years). The probabilities of 5-year overall survival (OS) and leukemia-free survival (LFS) were 59.3% and 55.5%, respectively. Multivariate analysis identified the following unfavorable survival factors: infused total nucleated cell dose<314 x 10(6) /kg (relative risk [RR]=2.43; 95% confidence interval [CI]=1.33-4.44; P=.004), advanced phase (RR=2.43; 95% CI=1.37-4.31; P=.004), and no major cytogenetic response (MCyR) at the time of BMT (RR=6.55; 95% CI=1.98-21.6; P=.002). Of the 17 patients treated with imatinib, 15 (88%) achieved MCyR at the time of BMT, and this group had an excellent 5-year OS of 81.9%. Disease phase, infused total nucleated cell dose, and cytogenetic response were independent risk factors for survival of unrelated BMT. These findings provide important information for assessing the indications for and improving outcome in unrelated BMT for the treatment of pediatric CML.

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

NKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor. The NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program. In patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p=0.02), but had no impact on disease relapse or the development of grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease. These data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.

Transplantation of Unrelated Donor Umbilical Cord Blood for Nonmalignant Diseases: a Single Institution's Experience with 45 Patients

The potential benefits of unrelated donor bone marrow transplantation are offset by the immunologic complications of graft-versus-host disease (GVHD) and infection. We used cryopreserved umbilical cord blood (UCB) as a strategy to reduce the risks of GVHD and treatment-related mortality (TRM) and improved survival. Data on 45 patients with median age of 4.5 years who received transplants between October 2003 and February 2009 for the treatment of nonmalignant diseases were evaluated. As of May 15, 2009, the median follow-up was 25 months (range: 3-66). The majority (82%) of patients received an HLA-mismatched graft. The median infused total nucleated cell dose was 7.6 x 10(7)/kg and CD34(+) count 4.0 x 10(5)/kg. Primary graft failure was encountered after 4 transplantations (8%). Log-rank tests and Cox regression analyses were used to determine the effects of various demographic, graft-related, and treatment factors on engraftment, GVHD, TRM, graft failure, and survival. Incidences of neutrophil and platelet engraftment were 88% and 82%, respectively. The incidence of severe grade III-IV acute GVHD (aGVHD) was 42%. Five-year overall survival (OS) and disease-free survival (DFS) were 88.1% and 77.1%, respectively. The cumulative incidence of TRM at 2 years was 12.0%. When cell dose and other factors are optimal, unrelated CBT is a promising approach for curative therapy of nonmalignant diseases.

Successful allogeneic bone marrow transplantation for myelodysplastic syndrome complicated by severe pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the abnormal accumulation of alveolar surfactant protein in alveolar spaces. We report herein a rare case of myelodysplastic syndrome (MDS-RAEB) complicated by severe PAP, and successful allogeneic bone marrow transplantation (BMT) for both disorders. An unrelated BMT was planned for a 48-year-old male with advanced MDS-RAEB. Just before the initiation of the conditioning regimen for unrelated BMT in March 2007, he developed dyspnea. A diagnosis of PAP was made based on findings of chest X-ray, CT scanning, and the fluid obtained by bronchoalveolar lavage. To improve his dyspnea and improve BMT safety, whole lung lavage (WLL) was performed twice, with the partial improvement of PAP. Unrelated allogeneic BMT was performed in September 2007. We had to perform a third WLL because of the worsening of PAP on day 26 after BMT. Despite many infectious complications after BMT, GVHD was relatively mild. PAP had almost disappeared 6 months after BMT. He was well with favorable hematopoiesis 20 months after the BMT without any specific treatment. There has been no report of an MDS patient with PAP in whom 3 WLL procedures were performed before and after allogeneic BMT.

非血縁者間骨髄移植後TLS/FUS-ERG mRNAが消失したにもかかわらず再発を来したt(16;21)(p11;q22)-AML (M7)

非血縁者間骨髄移植後TLS/FUS-ERG mRNAが消失したにもかかわらず再発を来したt(16;21)(p11;q22)-AML (M7)

Reduced-intensity conditioning regimens before unrelated cord blood transplantation in adults with acute leukaemia and other haematological malignancies

Cord blood is an unlimited source of haematopoietic stem cells for allogeneic haematopoietic stem cell transplants. During the past 5 years, the number of adults transplanted with cord blood cells from unrelated donors has exceeded the number of transplants in children, as a result of better definitions of cord blood unit choice, an increased number of cord blood units available for transplantation worldwide, comparable results of unrelated cord blood transplantation (UCBT) with human leukocyte antigen-matched unrelated bone marrow transplantation, the use of double cord blood transplantation and the use of UCBT after a reduced-intensity conditioning (RIC) regimen. In spite of the encouraging results of RIC UCBT in single-centre studies, the number of patients given this strategy is still limited and follow-up is still too short to draw definitive conclusions. Moreover, many questions remain to be answered such as: (1) the type of patients and disease populations that may benefit most from this strategy; (2) the best conditioning regimen to use; (3) the criteria of cord blood choice in this setting; and (4) factors predictive of outcomes after RIC UCBT. This paper will summarize some recent results of RIC UCBT for adults with haematological malignancies.

Clinical analysis of six children with aplastic anemia after allogeneic hematopoietic stem cell transplanta-tion

Objective To explore the efficacy of allogeneic hematopeietic stem cell transplantation in children with aplastic anemia. Methods In six children with aplastic anemia, five children received G-CSF primed allogeneic bone marrow plus peripheral stem cell transplantation from HLA-matched siblings, the nucleat- ed cell dose of BM and PBSC transplanted was respectively 4. 61 ( 1.5 ～ 13.2)×108/kg and 9. 36(2. 05 ～ 16. 75 )×108/kg. All five cases used FLU + CTX + ATG as the conditioning regimens. One child received unre-lated HLA-matched bone marrow transplantation, the nucleated cell dose of BM transplanted was 16. 8 x 10S/kg, and used FLU + CTX + TBI as the conditioning regimen. All cases received CSA + MTX + MMF as acute GVHD prophylaxis. Results One child got graft failure and the hematopoiesis recovered at 23 days by itself. The other five children achieved hematopoietic recovery after transplantation. None of them got GVHD after transplanta-tion. One child who had got MAA for four years happened graft rejection,got disease recurrence and finally died of serious infection. Other five children got disease-free survival with a follow-up to Feb 2009. Conclusion AI-logeneic bone marrow plus peripherial stem cell transplantation from HLA-matched siblings could be considered as the preferred treatment for children with aplastic anemia. It is feasible for children with aplastic anemia to re-ceive bone marrow transplant from unrelated HLA-matched donors when the patient was failed in immunosup-pressive therapy and without an available sibling donor. Key words: Hematopeietic stem cell transplantation; Aplastic anemia; Children

Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning

We evaluated the efficacy of a post-grafting immunosuppressive regimen consisting of tacrolimus, methotrexate, and mycophenolate mofetil (MMF) in 21 adults (median age, 55 years) with poor-risk hematologic malignancy who underwent unrelated bone marrow transplantation after fludarabine-based reduced-intensity conditioning (RIC). In combination with intravenous tacrolimus and minidose methotrexate (5 mg/m2 on days 1, 3, and 6), MMF was orally administered at 30 mg/kg daily in three divided doses between days 7 and 27. All patients achieved neutrophil recovery with donor-type chimerism at a median of 19 days (range, 13-35). Cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 33% (95% CI, 15-53%) and 5% (95% CI, 0.3-20%), respectively. Five of 20 evaluable patients developed extensive chronic GVHD. Toxicities associated with the use of MMF were acceptable, although one patient experienced intractable GVHD immediately after the cessation of MMF. With a median follow-up of 24 months, overall survival at 3 years was 38% (95% CI, 14-63%). No late graft failure was observed. In conclusion, post-transplant MMF combined with tacrolimus and methotrexate was well tolerated and conferred stable donor cell engraftment, low risk of severe acute GVHD, and encouraging overall survival in unrelated donor marrow transplantation after RIC regimens.

Successful Prevention of Acute Graft-versus-Host Disease Using Low-Dose Antithymocyte Globulin after Mismatched, Unrelated, Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia

In this study, we investigated the effects of low-dose antithymocyte globulin (ATG, thymoglobulin) in the prevention of acute graft-versus-host disease (aGVHD) in mismatched, unrelated hematopoietic stem cell transplantations (uHSCTs) in patients with the single disease entity of acute myelogenous leukemia (AML). Patients (n = 103) with a variable risk for AML who received uHSCTs from available Asian and Caucasian donors were enrolled. First, we compared HLA-matched (group 1, n = 54) and HLA-mismatched (group 2, n = 49) transplantation patients. Then, we divided the patients in group 2, who had received transplants from allele(s)/antigen-mismatched donors, into 2 subgroups: patients who used ATG (group 3, n = 24) and those who did not (group 4, n = 25). To prevent the development of aGVHD, the patients in group 3 received ATG at a dose of 1.25 mg/kg body weight per day for 2 consecutive days, together with our standard regimen of methotrexate (MTX) and tacrolimus. The median CD34(+) cell infusion was 4.2 x 10(6)/kg (range: 1.2-34.4). The median patient age was 41 years (range: 16-57), and the median follow-up duration of patients who were event-free survivors was 23 months (range: 2-72). The overall incidences of aGVHD and chronic GVHD (cGVHD) were 38% and 56%, respectively. Of 48 evaluable patients in group 2, 10 (21%) developed moderate to severe aGVHD (grades II-IV). In contrast, 2 (8%) of the 24 patients in group 3 and 7 (29%) of the 24 evaluated patients in group 4 required therapy for aGVHD (grades II-IV; P = .038). The incidence of cGVHD was not different between groups 3 and 4. The estimated probabilities of overall survival (OS) and event-free survival (EFS) at 2 years for group 2 were 55% and 44%, respectively. In comparison, the estimated probabilities of OS and EFS at 2 years for groups 3 and 4 were 68% versus 38% (P = .043) and 58% versus 38% (P = .103), respectively. The overall cumulative incidence of nonrelapse mortality (NRM) was 29% in group 2. The cumulative incidence of NRM differed markedly between group 3 (16%; 95% confidence interval [CI], 4%-28%) and group 4 (44%, 95% CI, 34%-54%) (P = .013). We found no difference in cytomegalovirus (CMV) reactivation between groups 3 and 4. These results suggest that in mismatched uHSCT, a low dose of ATG (total 2.5 mg/kg) may prevent moderate to severe aGVHD, with comparable rates of relapse and CMV reactivation and a greatly decreased rate of NRM.

Unrelated umbilical cord blood transplantation and unrelated bone marrow transplantation in children with hematological disease: A meta‐analysis

UCB has been used as an alternative source of HSC. Both unrelated donor BM and UCB are available as potential options for transplantation. However, there have been limited comparisons of the outcomes of unrelated donor UCBT vs. UBMT in the unrelated setting. Our aim is to observe the therapeutic efficacy of UCBT and UBMT for treatment of pediatric hematological diseases. We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and critically appraised all relevant articles (1989.1-2008.5). Comparative studies were carried out on clinical therapeutic effect of UCBT and UBMT with research on stem cells engraftment, complications, earlier mortality, and survival rate. We performed a meta-analysis using review manager 5.0 software (RevMan, The Nordic Cochrane Center, The Cochrane Collaboration) and adopted funnel plot regression to assess the publication bias. We obtained 324 records. Seven trials totaling 1453 patients have been assessed. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of engraftment failure and earlier transplantation-related mortality were higher with UCBT because of its delay of hematological recovery [OR = 4.96, 95% CI (3.25, 7.59), p < 0.00001 and OR = 2.36, 95% CI (1.79, 3.11), p < 0.00001 respectively], but CMV infection didn't increase obviously. There was no difference in long disease-free survival rate [OR = 0.85, 95% CI (0.65, 1.01), p = 0.06] between UCBT and UBMT due to the decrease of GVHD in UCBT [OR = 0.45, 95% CI (0.34, 0.60), p < 0.0001]. Our meta-analysis confirmed that UCBT in children is also an effective way to treat children with hematological disease and has equivalent survival outcomes compared with UBMT.