Letermovir prophylaxis reduced cytomegalovirus reactivation and resistance post umbilical cord blood transplantation.

To explore the impact of letermovir (LET) prophylaxis on cytomegalovirus (CMV) reactivation and resistance in both adult and paediatric umbilical cord blood transplantation (UCBT) patients, we retrospectively compared 43 UCBT patients who received LET as CMV prophylaxis with a historical cohort of 207 UCBT patients without LET usage. LET was administered from Day +1 to Day +100. The 180-day cumulative incidence of CMV reactivation (47.3% vs. 74.4%, p < 0.001) and the proportion of refractory CMV reactivation (15.0% vs. 42.9%, p = 0.016) were significantly lower than those in the control group. However, more frequent late CMV infection (31.0% vs. 4.3%, p = 0.002) and the 180-day cumulative incidence of Epstein-Barr virus (EBV) reactivation (9.3% vs. 3.4%, p = 0.087) were observed in UCBT patients with LET prophylaxis. Meanwhile, older age (>15 years old) and the occurrence of pre-engraftment syndrome were identified as the significant risk factors for CMV reactivation, and in patients at high risk, the incidence of CMV reactivation in the LET group was lower than that in the control group (46.7% vs. 86.5%, p < 0.001), while this decline was less pronounced among patients at low risk (47.8% vs. 62.1%, p = 0.120).

The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases.

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.

Poor survival and prediction of prolonged isolated thrombocytopenia post umbilical cord blood transplantation in patients with hematological malignancies.

Prolonged isolated thrombocytopenia (PIT) is a common complication after umbilical cord blood transplantation (UCBT). However, data on PIT prediction and impacts on transplantation outcomes for UCBT patients are rare. We retrospectively analyzed 244 patients with hematological malignancies who received single-unit UCBT at the First Affiliated Hospital of USTC between August 2018 and December 2019. Among them, PIT occurred in 49 recipients, with a crude incidence of 20.1%. In the PIT patients, the 2-year cumulative incidence of transplant-related mortality (TRM) was significantly higher, and the probabilities of 2-year overall survival, leukemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were significantly poorer (57.1% vs. 88.6%; 53.1% vs. 81.9%; 22.4% vs. 59.8%; p < 0.001), without remarkable increases in the cumulative incidence of relapse or chronic GVHD. Importantly, the multivariate analysis revealed that lower high-resolution HLA compatibility (≤6/10), lower infused CD34+ cell count (≤1.78 × 105 /kg), grade II-IV acute GVHD preplatelet engraftment, a lower pretransplantation platelet count (≤100 × 109 /L), and a longer neutrophil engraftment time (≥17 days) were independent risk factors for PIT after UCBT. These results demonstrate that PIT is common after UCBT, predicting inferior survival and the need for more monitoring during the early phase.

Clinical outcome of cord blood transplantation for nine children with juvenile myelomonocytic leukemia receiving fludarabine-busulfan-cyclophosphamide-based conditioning.

BACKGROUND: Juvenile myelomonocytic leukemia (JMML) is a rare hematological malignancy in young children and can only be cured through the allogeneic stem cell transplantation. PROCEDURE: We have retrospectively analyzed the outcomes of nine children with JMML after unrelated cord blood transplantation (UCBT). RESULTS: Eight patients who have received a myeloablative conditioning regimen of fludarabine (FLU), busulfan (BU), and cyclophosphamide (CY) have gotten engraftment. None of the nine patients has relapsed following initial UCBT. Six patients are still alive and in complete remission after UCBT with a median observation time of 43 months (range: 10-80 months). CONCLUSIONS: This study shows that UCBT with FLU-BU-CY conditioning regimen can represent a suitable option for children with JMML.

Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival.

This is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1-2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4-89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89-37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0-83.6%), which was significantly higher than the 10% (95% CI, 5.72-35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0-46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8-98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0-41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2-76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

Outcomes of Adolescents and Young Adults Compared with Children with Acute Leukemia after Single-Unit Unrelated Cord Blood Transplantation Using Myeloablative Conditioning without Antithymocyte Globulin.

BACKGROUND: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain. METHODS: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG). RESULTS: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. The 30-day cumulative incidence of neutrophil engraftment was similar between AYAs and children, but children had faster rates of neutrophil and platelet recovery than AYAs. The median time to neutrophil engraftment was earlier in children than in AYAs (AYAs, 19 days, 95% confidence interval [CI] 17.3-21.7; children, 16 days, 95% CI 13.1-19.5, p = 0.00003). The incidence of platelet recovery on day 120 was higher in children than in AYAs (AYAs, 80%, 95% CI 71-81%; children, 88%, 95% CI 82-92%, p = 0.037). CD34+ cell dose was the only independent factor influencing both neutrophil and platelet recovery. The cumulative incidence of NRM at 2 years was higher among AYAs than among children (AYAs, 27.5%, 95% CI 20-37%; children, 15%, 95% CI 10-21%, p = 0.008). Conditioning regimen was an independent factor influencing NRM. With respect to immune reconstitution, natural killer cell counts quickly recovered to normal levels 1-month post-CBT in both children and AYAs. CD8+ T-cell counts were higher in children than in AYAs at 1 and 3 months post-CBT. CD4+ T-cell counts were similar in both children and AYAs after CBT. CONCLUSION: AYAs with acute leukemia have outcomes of single-unit CBT using MAC without ATG that are as good as those of children. Thus, single-unit CBT using modified MAC without ATG is an acceptable choice for both AYAs and children who do not have a suitable donor.

Effects and long-term follow-up of using umbilical cord blood-derived mesenchymal stromal cells in pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis after unrelated cord blood transplantation.

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×108 /mL before MSC infusion and 2.67 (0-56.3) ×108 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.

Decitabine prior to salvaged cord blood transplantation for acute myeloid leukaemia/myelodysplastic syndrome not in remission.

WHAT IS KNOWN AND OBJECTIVE: Many refractory/relapsed haematological malignancies, in non-remission state, still have poor prognosis even after allogeneic haematopoietic stem cell transplantation. Recently, decitabine or umbilical cord blood transplantation (UCBT) seemed to be effective in these patients. However, few studies have added decitabine to myeloablative conditioning regimens for UCBT in patients with haematological malignancies not in remission. Therefore, the objective was to evaluate the clinical outcomes of patients with refractory/relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) using decitabine as part of a myeloablative conditioning regimen prior to salvaged unrelated UCBT at our centre. METHODS: We enrolled 20 consecutive patients with refractory/relapsed AML/MDS between 2013 and 2018. All patients were in non-remission state before transplantation. All transplants were performed with decitabine as part of the myeloablative conditioning regimen, which was decitabine + fludarabine/busulfan/cyclophosphamide. RESULTS AND DISCUSSION: All patients achieved neutrophil and platelet engraftment. Incidence of grade III/IV acute graft-vs-host disease (GVHD) was 20.0%, which was also decreased compared to non-decitabine group (P = .025). The median follow-up time after UCBT was 29 months (range 14-64 months). The 2-year probability of GVHD-free relapse-free survival (GRFS) was higher in the decitabine group. Univariate showed that the decitabine group was associated with a higher GRFS than the non-decitabine group. The estimated probability of overall survival and relapse was 55% and 20.0%, respectively. WHAT IS NEW AND CONCLUSIONS: Our results suggest that addition of decitabine as part of the myeloablative conditioning regimen prior to UCBT for refractory/relapsed AML/MDS in patients who are not in remission is safe and might be an effective treatment option.

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study.

Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall survival (OS) and disease free survival (DFS) were significantly higher in the MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p = 0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we conducted a prospective single-arm clinical trial including 188 patients who underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of the MMAC group in the prospective trail (MMAC-P) were similar to the MMAC group in the retrospective study (MMAC-R). This study is the first to demonstrate the superiority of MMAC to MAC in CBT for hematological malignancies.

The incidence, risk factors and outcomes of early bloodstream infection in patients with malignant hematologic disease after unrelated cord blood transplantation: a retrospective study.

BACKGROUND: Bloodstream infection (BSI) is one of the major causes of morbidity and mortality for patients undergoing hematopoietic stem cell transplantation (HSCT). The unrelated cord blood transplantation (UCBT) can provided opportunities for patients without suitable donors for bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT), while few studies have addressed BSI after UCBT. The aim of this study was to analyse the incidence and risk factors of BSI, causative organisms, microbial resistance, and its impact on the clinical outcomes and survival of patients. METHODS: There are 336 patients, were divided into two groups depending on whether developing BSI. Demographic characteristics, laboratory data, and clinical outcome were compared between different groups. The risk factors of BSI was examined using logistic regression and the survival was examined using the Kaplan-Meier method and log-rank test. RESULTS: Ninety-two patients (27.4%) developed early BSI with 101 pathogenic bacteria isolated, and the median day of developing initial BSI was 4.5 d. Gram-negative bacteria were the most common isolate (60, 59.4%), followed by Gram-positive bacteria (40, 39.6%) and fungi (1, 1.0%). Thirty-seven (36.6%) isolates were documented as having multiple drug resistance (MDR). Myeloid malignancies, conditioning regimens including total body irradiation (TBI), and prolonged neutropenia were identified as the independent risk factors for early BSI. The 3-year OS was 59.9% versus 69.2% in the BSI group and no-BSI group (P = 0.0574), respectively. The 3-year OS of the MDR group was significantly lower than that of the non-BSI group (51.1% versus 69.2%, p = 0.013). CONCLUSIONS: Our data indicate that the incidence of early BSI after UCBT was high, especially in patients with myeloid disease and a conditioning regimen including TBI and prolonged neutropenia. Early BSI with MDR after UCBT had a negative impact on long-term survival.

European Group for Blood and Marrow Transplantation Risk Score Predicts the Outcome of Patients with Acute Leukemia Receiving Single Umbilical Cord Blood Transplantation.

The European Group for Blood and Marrow Transplantation (EBMT) risk score has been implemented as an important tool to predict patient outcomes after allogeneic hematopoietic stem cell transplantation. However, to our knowledge, this score has never been applied in cases of single umbilical cord blood transplantation (sUCBT). We retrospectively analyzed 207 consecutive patients with acute leukemia who received sUCBT at our center between February 2011 and December 2015. The probabilities of 3-year overall survival (OS) and leukemia-free survival (LFS) of the entire cohort were 65.0% and 59.8%, respectively, whereas the cumulative incidences of 3-year nonrelapse mortality (NRM) and relapse rate were 19.5% and 20.3%, respectively. In the univariate analysis, a higher EBMT risk score was associated with worse OS and LFS and higher NRM and relapse rate, ranging from 81.7%, 75.9%, 7.3%, and 15.3%, respectively, for patients with a score of 1 to 43.8%, 44.3%, 31.7%, and 23.9%, respectively, for patients with scores of 4 to 6. Hazard ratios of OS, LFS, and NRM all steadily increased for each additional score point. Importantly, the prognostic value of the EBMT risk score on OS, LFS, NRM, and relapse was maintained in the multivariate analysis. Moreover, considering the univariate analysis results of donor-recipient gender and mismatched allele-level HLA-A, -B, -C, and -DRB1 loci on patient outcomes and the fairly strong interaction between time from diagnosis to sUCBT and disease status, we developed a modified sUCBT-EBMT risk score by using degrees of 8-allele HLA match instead of donor type, donor-recipient gender combination, and time from diagnosis to sUCBT, and found that the modified score could also be used as a predictor for patient outcomes after sUCBT. The EBMT risk score is a good predictor of outcomes of patients with leukemia after sUCBT. The modified sUCBT-EBMT risk score can also be used as a pretransplant risk assessment, but this metric still requires further evaluation with a larger cohort.

Umbilical Cord Blood Transplantation without Antithymocyte Globulin Results in Similar Survival but Better Quality of Life Compared with Unrelated Peripheral Blood Stem Cell Transplantation for the Treatment of Acute Leukemia-A Retrospective Study in China.

Although previous studies have demonstrated improved outcomes in umbilical cord blood transplantation (UCBT) by omitting antithymocyte globulin (ATG) in the conditioning regimen, this approach has not been comparatively studied in unrelated peripheral blood stem cell transplantation (UPBSCT). To compare the risks and benefits between UCBT without ATG and UPBSCT in patients with acute leukemia (AL), we conducted a multicenter retrospective study of 79 patients who underwent UCBT (myeloablative conditioning without ATG) and 96 patients who underwent UPBSCT (myeloablative conditioning with ATG). The outcomes were graft failure, neutrophil engraftment, platelet engraftment, acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), transplantation-related mortality (TRM), relapse, overall survival (OS), and leukemia-free survival (LFS). Follow-up was censored on October 31, 2016. Engraftment was similar between the 2 groups but granulocyte and platelet recovery were slower in the UCBT group (both P < .001). The incidences of aGVHD, TRM, OS, and LFS were similar between the 2 groups (all P > .05). Without ATG, the UCBT group displayed less cGVHD and less moderate and severe cGVHD (P < .001 and P = .004). The incidences of Epstein-Barr virus viremia and post-transplantation lymphoproliferative disease were significantly lower in the UCBT group (P < .001 and P = .037). UCBT recipients had higher activity Karnofsky performance scores and 3-year GVHD-free/relapse-free survival than the UPBSCT group (P = .03 and P = .04). We observed similar survival when comparing UCBT without ATG and UPBSCT, but we also observed better quality of life in patients undergoing UCBT without ATG. We can therefore conclude that patients with primary AL for whom an appropriate HLA-matched sibling donor is not available could select either UCBT or UPBSCT.

Pre-engraftment bloodstream infections in acute leukemia patients undergoing unrelated cord blood transplantation following intensified myeloablative conditioning without ATG.

The aim of this study is to investigate the impact of pre-engraftment bloodstream infections (BSIs) on the outcomes in acute leukemia patients undergoing myeloablative cord blood transplantation (CBT). A total of 226 acute leukemia patients who received unrelated CBT were enrolled in this study, and all these patients received an intensified myeloablative conditioning without ATG. Pre-engraftment BSIs occurred in 72 patients (31.9 %), and the median time of onset was 4.5 days after cord blood infusion, BSIs of gram-negative bacilli, and gram-positive cocci comprised of 63.8 and 36.2 %, respectively. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic graft versus host disease (GVHD) were comparable among the non-BSI, gram-negative bacilli BSI, and gram-positive cocci BSI groups. The cumulative incidence of transplant-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) was similar between the non-BSI and the BSI groups. For subgroups analysis, TRM was lower in gram-positive cocci BSI patients compared with that of gram-negative bacilli BSI patients (8.3 vs 39.3 %) (p = 0.01) (HR = 0.39, p = 0.034), and the 5-year OS was higher in gram-positive cocci BSI cohort (79.1 vs 44.2 %) (p = 0.01) (HR = 0.36, p = 0.046). Our study demonstrated that, for acute leukemia patients who received CBT after myeloablative conditioning that omitted ATG, pre-engraftment BSI had no impact on engraftment, GVHD, TRM, relapse, and long-term survival. Due to the fact that gram-negative bacilli BSI was associated with poor outcomes compared with gram-positive cocci BSI, appropriate early empirical antimicrobial management strategies and better supportive care are required to decrease the gram-negative bacilli BSI-related mortality.

Comparison of outcomes after umbilical cord blood and unmanipulated haploidentical hematopoietic stem cell transplantation in children with high-risk acute lymphoblastic leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with high-risk acute lymphoblastic leukemia (ALL). Human leukocyte antigen (HLA)-haploidentical HSCT (haplo-HSCT) or umbilical cord blood transplantation (UCBT) are both important alternative sources of stem cells for those without an HLA-identical sibling donor or unrelated matched donor. We aimed to compare the therapeutic effects of single UCBT and unmanipulated haplo-HSCT in high-risk ALL children (n = 129). Hematopoietic recovery was significantly faster in haplo-HSCT recipients than in UCBT recipients. The 2-year cumulative incidences of relapse in the haplo-HSCT and UCBT groups were 16.1% and 24.1%, respectively (p = 0.169). The 2-year cumulative incidences of non-relapse mortality in the haplo-HSCT and UCBT groups were 12.8% and 18.8%, respectively (p = 0.277). The 2-year probabilities of overall survival in the haplo-HSCT and UCBT groups were 82.0% and 69.6%, respectively (p = 0.071), and the 2-year probability of disease-free survival in the haplo-HSCT group was higher than in the UCBT group (71.0% vs. 57.2%, p = 0.040). However, several variables (such as leukocyte count and cytogenetics at diagnosis) were different between the groups, and a possible center effect should also be considered. In addition, only mild and moderate chronic graft-versus-host disease (GVHD) was associated with significantly improved survival compared to those without chronic GVHD in multivariate analysis. Thus, our results show that both unmanipulated haplo-HSCT and UCBT are valid for high-risk ALL children lacking a HLA matched donor, and both strategies expand the donor pool for children in need.

Decitabine prior to salvaged unrelated cord blood transplantation for refractory or relapsed childhood acute leukemia.

No clinical studies have investigated the role of decitabine as a part of the myeloablative conditioning regimen prior to UCBT for refractory or relapsed childhood AL in patients in NR status. The aim of this study was to identify the potential benefits of decitabine as a prior therapy before salvaged unrelated UCBT for refractory or relapsed childhood AL. Eight consecutive patients with childhood refractory/relapsed AL were enrolled in our study between 2013 and 2014. All patients were in NR status before the time of transplant and had features associated with poor outcomes, such as CNSL, MDS-AML, high WBC count at diagnosis, and hypodiploid status (FLT3+/ITD+). Additionally, all patients had one of the following disease statuses: PIF, multiple relapse, or early relapse. All transplants were performed with decitabine as part of the myeloablative conditioning regimen, which was decitabine+Flu/Bu/CY±BCNU or decitabine+Ara-c/BU/CY2±BCNU. A total of seven patients (7 of 8) achieved neutrophil engraftment and platelet engraftment, and one patient experienced primary graft failure. All eight patients (100%) developed PES at a median of 7 days. Three patients developed stage II-IV acute GVHD at a median of 18 days. Additionally, three patients developed chronic GVHD, but it was not extensive in any of those three patients. The median follow-up time after CBT was 19.9 months (range, 9.2-30.7 months). The estimated probability of OS was 75%. Two patients (2 of 8) experienced a testis relapse, and two patients (2 of 8) died. Our experience suggests that the additional application of decitabine as part of the myeloablative conditioning regimen prior to UCBT for refractory or relapsed childhood AL among patients who are not in remission is safe and might be an effective treatment option.

[The curative efficacy of unrelated umbilical cord blood stem cells transplantation in intensified myeloablative conditioned patients with acute lymphoblastic leukemia].

OBJECTIVE: To retrospectively analyze the efficacy of unrelated umbilical cord blood transplantation (UCBT) with intensified myeloablative conditioning regimen in patients with acute lymphoblastic leukemia (ALL). METHODS: From September 2006 to December 2013, a total of 110 consecutive patients with ALL had received UCBT, including 79 male and 31 female patients with a median age of 14(2-51) years, a median weight of 45(12-100)kg. Sixty-one cases were in the first complete remission (CR), 30, 6 and 13 patients in the second, the third CR and advanced stages respectively. The conditioning regimen consisted of total body irradiation, cyclophosphamide and cytarabine (TBI/Cy/Ara-C) in 61 patients, busulfan, cyclophosphamide and fludarabine (BU/Cy/Flu) in 39 patients and BU/Cy/Ara-C in 10 patients. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: The median amount of total nuclear cells(TNC) and CD34(+) cells were 3.90(1.97-13.50)×10(7)/kg and 2.07(0.40-5.56)×10(5)/kg. The cumulative incidence of sustained donor engraftment was 94.5% (95% CI 94.5%-94.6%) at a median of 18 days after transplantation (range, 12-37 days). The cumulative incidence of platelet recovery at 180 days after transplantation was 82.1% (95% CI 81.8%-82.4%) with a median time to recovery of 40 (range, 15-153) days. Incidences of grade Ⅱ~Ⅳ and Ⅲ~Ⅳ acute GVHD were 21.8% and 10.9% respectively. The cumulative incidence of chronic GVHD was 17.9%. During a median follow up period of 26 (range 6-94) months, the disease free survival (DFS) and overall survival (OS) rates at 3 years were 54.5% and 58.8%, respectively. The transplantation-related mortality (TRM) at 180 days after transplantation was 22.7%. The cumulative incidence of 3-year relapse rate was 18.3% (95% CI 17.9%-18.6%). CONCLUSIONS: UCBT with intensified myeloablative conditioning regimen not only improves the donor engraftment, but also shortens the interval of neutrophil and platelet recovery. It is a safe and effective option for children and adult ALL patients lack of matched related donors.

Comparative analysis of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation in children with high-risk or advanced acute leukemia.

The aim of this report was to present a clinical comparison of unrelated cord blood transplantation (CBT) and human leukocyte antigen (HLA)-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) in children with high-risk or advanced acute leukemia. A total of 115 consecutive pediatric patients received unrelated CBT (n = 90) or sibling allo-PBSCT/BMT (n = 25) between 2000 and 2012. Neutrophil and platelet recovery were significantly delayed after CBT compared to allo-PBSCT/BMT. There was no difference in the incidence of acute graft-versus-host disease (GVHD) or chronic GVHD between the two groups. The cumulative incidence of transplant-related mortality (TRM) was higher in the CBT group than in the allo-PBSCT/BMT group (32.5 vs 12.8 %) (p = 0.03). The cumulative incidence of relapse was 13.1 % after CBT, which was significantly lower than that of after allo-PBSCT/BMT (45.3 %) (p = 0.015). The overall survival (OS) and leukemia-free survival (LFS) in the CBT group were similar to those of the allo-PBSCT/BMT group; however, for acute myeloid leukemia (AML) patients, the 5-year LFS in the CBT group was slightly better than the allo-PBSCT/BMT group (55.7 % for CBT and 32.7 % for allo-PBSCT/BMT) (p = 0.08). Our comparisons suggest that for high-risk or advanced childhood acute leukemia, unrelated CBT has a higher TRM and similar long-term survival, but better antileukemia effect than HLA-matched sibling PBSCT/BMT. New strategies and better supportive care are required to decrease the TRM of CBT.

A novel mutation in Wiskott-Aldrich syndrome and successfully treated with umbilical cord blood transplantation.

We report a novel mutation in a boy with Wiskott-Aldrich syndrome (WAS) who was 4 years and 10 months of age and underwent successful umbilical cord blood transplantation (UCBT). The child presented at 3 months of age with symptomatic thrombocytopenia and eczema. Despite a large dose of intravenous immunoglobulin treatment, no increase in the platelet count was observed. A genetic analysis revealed a deletion mutation at c.410_419del10 in exon 4, which resulted in the replacement of encoded phenylalanine with serine at amino acid 137 and caused an early stop codon at downstream amino acid 121 (p.F137SfsX121), and confirmed a diagnosis of WAS. The only curative treatment for WAS is hematopoietic stem cell transplantation. Because no matched sibling donor was available, he underwent unrelated UCBT. He is currently alive and doing well at fourteen months post-transplant, and he is free of any bleeding episodes. The eczema that was all over his body had disappeared. This case suggests that unrelated UCBT may be safe and technically feasible for the treatment of WAS when an appropriately matched related or unrelated donor is unavailable.