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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The impact of pretransplant minimal residual disease (MRD) on outcome of myeloablative cord blood transplant (CBT) for acute myeloid leukemia (AML) in complete remission (CR) has not been reported. Seventy-two AML patients were assessed for MRD before CBT, and the majority (84.7%) of these patients received single-unit CBT. All patients received intensified myeloablative conditioning with BUCY2 or TBICY plus high-dose cytarabine, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic GVHD were comparable between MRD-negative and MRD-positive groups. The cumulative incidence of transplant-related mortality (TRM) and relapse did not differ significantly between the two cohorts (25.6% vs. 32.5%, 16.1% vs. 19.2%;p = 0.52, 0.61). There were no apparent differences in 3-year overall survival (OS) (68.9% in MRD-negative group and 57.9% in MRD-positive group,p = 0.31) and 3-year leukemia-free survival (LFS) (62.5% in MRD-negative group and 52.7% in MRD-positive group,p = 0.42) between both groups. The current study suggests that AML patients in morphological CR1 or CR2 who have detectable MRD might benefit from unrelated CBT with intensified myeloablative conditioning. [ABSTRACT FROM AUTHOR]

Pre-engraftment syndrome (PES) after umbilical cord blood transplantation (CBT) remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcomes of PES in CBT recipients, who had been treated for hematologic malignancies at our transplantation center. PES was defined as unexplained fever higher than 38.3°C that is not associated with documented infection and unresponsive to antimicrobial manipulations and/or unexplained erythematous skin rash occurring prior to neutrophil engraftment. A total of 81 patients (median 18 yr, range 3-48) received either myeloablative ( n = 72) or non-myeloablative ( n = 9) conditioning. Neutrophil engraftment was achieved in 69 of the 81 cases [86.2%, 95% confidence interval (CI) = 78.9-94.1%], and the median time to more than 0.5 × 109/L ANC was 19 d (range, 12-39). Fifty-one patients (63.0%) developed PES at a median of 7 d (range 3-15) post-transplant: 46 patients had both rash and unexplained fever; one patient had unexplained fever alone; and four patients had rash only. Forty-seven patients (92.2%) received IV methylprednisolone (MP) at a median dose of 1 mg/kg (range 0.4-3). All patients treated with MP responded as evidenced by fever resolution combined with resolution of rash. All patients with PES had high serum levels of C-reactive protein (CRP), which were significantly reduced after effective steroid treatment. Univariate analysis identified myeloablative conditioning and younger age as significant risk factors for developing PES. Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) in the PES+ and PES− groups was 51.5% (95% CI = 38.0-70.0%) and 17.0% (95% CI = 6.9-41.7%), respectively. In a multivariate analysis, we found significantly increased risk of grade II-IV aGVHD among PES patients ( P = 0.041). However, PES was not associated with sustained donor engraftment, the day to neutrophil recovery, chronic graft-versus-host disease, transplant-related mortality at day 180, and overall survival. Despite of the inherent limitations of this small retrospective study, PES seemed to be common after CBT and associated with high incidence of aGVHD. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease continues to be a major life-threatening complication after allogeneic hematopoietic stem cells transplantation (aHSCT). The relationship of acute GVHD (aGVHD) with the levels of peripheral CD4+CD25high T cells in patients after aHSCT and in their corresponding donors is not fully investigated. We examined the levels of CD4+CD25high T cells in patients after aHSCT and in their corresponding donors, and analyzed the relationship of CD4+CD25high T cells to the incidence and prognosis of aGVHD. The recipients with normal or high CD4+CD25high T cells (three of eight, 37.5%) had no or mild aGVHD (grade I), and all survived during the follow-up period. In striking contrast, the recipients with lower or no CD4+CD25high T cells suffered from greater than grade II aGVHD (four of four, 100%), and all died within 1-year post-aHSCT. Moreover, the number of CD4+CD25high T cells in recipients correlated significantly with that of their corresponding donors. The CD4+CD25high T cells from the recipients and their corresponding donors expressed high levels of Foxp3, and effectively suppressed the proliferation of CD4+CD25− responder T cells. This study suggests that human Treg cells may play an important role in aGVHD, as has been seen in murine models. The levels of peripheral CD4+CD25high T cells in recipients and donors could be helpful for predicting of the onset and outcome of aGVHD. [ABSTRACT FROM AUTHOR]

Abstract: This is the first report to present a clinical comparison of unrelated cord blood transplantation (CBT) and HLA-matched sibling allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia (CML) in advanced stage (accelerated phase or blast crisis). A total of 32 consecutive patients with advanced CML received unrelated CBT (n = 16) or HLA-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) (n = 16) between 2002 and 2011. The median day to neutrophil engraftment and the median day to platelet engraftment were longer in the unrelated CBT group. The cumulative incidence of grades 1 to 2 acute graft-versus-host disease (aGVHD), grades 3 to 4 aGVHD, and chronic graft-versus-host disease did not differ significantly between the 2 cohorts. The cumulative incidence of transplantation-related mortality (TRM) at day +180 was higher in CBT group (37.5% versus 12.5%, P = .013). The risk of relapse was lower in CBT patients compared with that of allo-PBSCT/BMT patients (14.2% versus 42.7%, P = .03). The long-term survival in CBT group patients was slightly better than that of allo-PBSCT/BMT group, although the difference did not reach statistical significance: the 5-year overall survival for CBT patients and allo-PBSCT/BMT patients was 62.5% and 48.6%, respectively (P = .10), whereas the 5-year leukemia-free-survival rate was 50% and 40.5%, respectively (P = .12). Our comparisons suggest that patients with advanced CML receiving unrelated CBT had a lower relapse rate, a slightly better long-term survival, but a higher early TRM than those receiving HLA-matched related allo-PBSCT/BMT. [Copyright &y& Elsevier]

Abstract: Graft-versus-host disease (GVHD) is a frequent and life threatening complication of allogeneic haematogenesis stem cell transplantation (aHSCT). The correlation of CD4+CD25+ regulatory T cells (Tregs) in the patients after aHSCT to the occurrence and severity of acute and chronic GVHD (aGVHD and cGVHD) is not fully investigated. Here, we examined the levels of CD4+CD25+ Tregs by assessment of CD4+CD25high and CD4+CD25+CD127low in peripheral blood, and the levels of serum TGF-β and TNF-α in 56 patients at early immune reconstitution following aHSCT. Our data showed a significant reduction in the frequency of Tregs in patients with grades II–IV aGVHD and extensive cGVHD compared to healthy controls. Moreover, a decreased level of CD4+CD25+ Tregs was correlated to increased severity of GVHD. The levels of CD4+CD25+ Tregs in non-GVHD groups were however significantly higher than that in healthy controls. A significant decrease in the levels of TGF-β and a significant increase the levels of TNF-α was also seen with increased severity of GVHD. This study suggested that measurement of CD4+CD25+ Tregs along with serum TGF-β and TNF-α at early immune reconstruction after aHSCT may indicate the onset and severity of both aGVHD and cGVHD. [ABSTRACT FROM AUTHOR]