Fei-Fei Tang

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III–IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1–23.1%) than in the ATG-10 group (4.5%, CI, 0.7–8.3%, P=0.005, 95% CI for the difference, −19.4% to −3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1–33.5%) than in the ATG-6 group (9.6% (4.0–15.2%), P=0.001). The 1-year disease-free survival rates were 84.3% (77.3–91.3%) and 86.0% (79.2–92.8%) for the ATG-6 group and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.

Controlled, Randomized, Open-Label Trial of Risk-Stratified Corticosteroid Prevention of Acute Graft-Versus-Host Disease After Haploidentical Transplantation

PURPOSE This study evaluated whether a prophylaxis strategy directed by the graft-versus-host disease (GVHD) biomarker might reduce the 100-day incidence of acute GVHD grades II to IV. PATIENTS AND METHODS This controlled, open-label, randomized trial included 228 patients who underwent haploidentical transplantation. On the basis of bone marrow allogeneic graft CD4:CD8 ratios, patients were categorized as low risk (n = 83; group A) or high risk (n = 145). Patients at high risk were randomly assigned to either receive (n = 72; group B) or not receive (n = 73; group C) low-dose corticosteroid prophylaxis. RESULTS The incidence in group B was 21% (95% CI, 11% to 31%) compared with 26% (95% CI, 16%to 36%; P = .43) in group A and 48% (95% CI, 32% to 60%; P < .001) in group C. Low-dose corticosteroid prophylaxis was significantly associated with a relatively low risk of acute GVHD grades II to IV (hazard ratio, 0.66; 95% CI, 0.49 to 0.89; P = .007) and rapid platelet recovery (hazard ratio, 0.30; 95% CI, 0.23 to 0.47; P < .001). The incidence of moderate-to-severe chronic GVHD in group B (21%) was lower than that in both group A (50%; P = .025) and group C (36%; P = .066). The 100-day corticosteroid doses were 205 ± 111 mg in group B, 229 ± 149 mg in group A (P = .256), and 286.54 ± 259.67 mg in group C (P = .016). Compared with group C, group B showed significantly lower incidences of femoral head necrosis (P = .034) and hypertension (P = .015). Infection rates were comparable among these groups. CONCLUSION Our results suggest that risk stratification-directed, low-dose corticosteroid prophylaxis significantly decreased the incidence of acute GVHD grades II to IV, accelerated platelet recovery, and reduced adverse events without increasing infections.

Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis.

BackgroundThis study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts.MethodsA retrospective study (n = 339) and a prospective study (n = 340) were performed. MRD was determined using multiparameter flow cytometry.ResultsEither after retrospective or prospective analysis, patients with negative pre-MRD (pre-MRDneg) had a lower incidence of relapse than those with positive pre-MRD (pre-MRDpos) in MSDT settings (P < 0.001 for all), but relapse was comparable in Haplo-SCT settings for patients with pre-MRDneg versus pre-MRDpos (P = 0.866 and 0.161, respectively). In either the retrospective (n = 65) or the prospective study (n = 76), pre-MRDpos subjects receiving Haplo-SCT experienced a lower incidence of relapse than those who underwent MSDT (P < 0.001 and p = 0.017, respectively). Of the patients with pre-MRDpos in either the total (n = 141) or the subgroup excluding cases which received donor lymphocyte infusion (DLI; n = 105), those who underwent MSDT had a higher incidence of relapse than those receiving haplo-SCT (P < 0.01 for all). Multivariate analysis showed that, for pre-MRDpos cases, haplo-SCT was associated with a low incidence of relapse and with better LFS and OS in either retrospective group, prospective group, combination groups, or subgroup not including cases which received DLI.ConclusionsThe results indicated that, for pre-MRD-positive AML patients, haplo-SCT was associated with lower incidence of relapse and better survival, suggesting a stronger anti-leukemia effect.

Combined model of the EBMT score modified model and the HCT-CI improves the stratification of high-risk patients undergoing unmanipulated haploidentical blood and marrow transplantation.

Abstract 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.

Monitoring of post-transplant CBFB-MYH11 as minimal residual disease, rather than KIT mutations, can predict relapse after allogeneic haematopoietic cell transplantation in adults with inv(16) acute myeloid leukaemia

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N‐acetyl‐L‐cysteine improves mesenchymal stem cell function in prolonged isolated thrombocytopenia post‐allotransplant

Prolonged isolated thrombocytopenia (PT) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Murine studies and in vitro experiments suggest that mesenchymal stem cells (MSCs) can, not only to support haematopoiesis, but also preferentially support megakaryocytopoiesis in bone marrow (BM). However, little is known about the quantity and function of BM MSCs in PT patients. In a case‐control study, we found that BM MSCs from PT patients exhibited significantly reduced proliferative capacities, increased reactive oxygen species and senescence. Antioxidant (N‐acetyl‐L‐cysteine, NAC) treatment in vitro not only quantitatively and functionally improved BM MSCs derived from PT patients through down‐regulation of the p38 (also termed MAPK14) and p53 (also termed TP53) pathways but also partially rescued the impaired ability of BM MSCs to support megakaryocytopoiesis. Subsequently, a pilot study showed that the overall response of NAC treatment was obtained in 7 of the enrolled PT patients (N = 10) without significant side effects. Taken together, the results indicated that dysfunctional BM MSCs played a role in the pathogenesis of PT and the impaired BM MSCs could be improved by NAC in vitro. Although requiring further validation, our data indicate that NAC might be a potential therapeutic approach for PT patients after allo‐HSCT.

Allogeneic hematopoietic cell transplantation for adult patients with treatment-related acute myeloid leukemia during first remission: Comparable to de novo acute myeloid leukemia

Therapy-related acute myeloid leukemia (T-AML) is associated with poor prognosis after conventional therapy. Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as a treatment for T-AML; however, data comparing outcomes of transplants for patients with de novo AML and T-AML are limited. Sixteen adult patients with T-AML during first complete remission after malignant disease received allo-HCT at the Peking University Institute of Hematology between January 1, 2006 and December 31, 2014. Eighty patients with de novo AML were selected using the case-pair method. The 3-year overall survival and leukemia-free survival for T-AML versus de novo AML patients were 66% vs. 79% (P=0.14) and 64% vs. 77% (P=0.13), respectively. The 3-year cumulative non-relapse mortality rates for T-AML versus de novo AML patients were 13% vs. 9% (P=0.47), respectively; the relapse rates were 20% vs. 13% (P=0.25), respectively. Our results suggest that the prognosis of T-AML is comparable to that of de novo AML after transplantation. Although T-AML shows poorer prognosis than de novo AML after conventional therapies, allo-HCT can markedly improve the prognosis of T-AML.

Dysfunctional Bone Marrow Mesenchymal Stem Cells in Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

Poor graft function (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by defective hematopoiesis. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis, but little is known about the role of MSCs in the pathogenesis of PGF. In the current prospective case-control study, we evaluated whether the number and function of bone marrow (BM) MSCs in PGF patients differed from those in good graft function (GGF) patients. We found that BM MSCs from PGF patients expanded more slowly and appeared flattened and larger, exhibiting more apoptosis and senescence than MSCs from GGF patients. Furthermore, increased intracellular reactive oxygen species, p-p53, and p21 (but not p38) levels were detected in MSCs from PGF patients. Moreover, the ability of MSCs to sustain hematopoiesis was significantly reduced in PGF patients, as evaluated by cell number, apoptosis, and the colony-forming unit-plating efficiency of CD34+ cells. In summary, the biologic characteristics of PGF MSCs are different from those of GGF MSCs, and the in vitro hematopoiesis-supporting ability of PGF MSCs is significantly lower. Although requiring further validation, our study indicates that reduced and dysfunctional BM MSCs may contribute to deficient hematopoiesis in PGF patients. Therefore, improvement of BM MSCs may represent a promising therapeutic approach for PGF patients after allo-HSCT.

Prevalence and risk factors of antibodies to human leukocyte antigens in haploidentical stem cell transplantation candidates: A multi-center study

We investigated the prevalence of and risk factors for antibodies to HLA in 1663 haploidentical transplant candidates. Among these cases, 349 (21.0%) showed positive panel-reactive antibody (PRA) either for class I or class II HLA. Multivariate analysis showed the following: i) risk factors associated with the prevalence of PRA either for class I or class II HLA were female gender (P = 0.018), prior transfusions (P < 0.001) or pregnancy (P < 0.001), and cases with MDS (P = 0.018); compared to other patients, subjects with ALL had a lower prevalence of class I antibodies (P = 0.017); and ii) risk factors associated with the prevalence of PRA both for class I and class II HLA were female gender (P = 0.014), prior transfusions (P = 0.003), previous pregnancy (P < 0.001), and diagnosis with MDS (P = 0.035). The percentages of antibodies against different antigens coded by the different HLA loci, including HLA-A, -B, -C, -DP, -DQ, and -DR, among all cases were 15.6%, 17.3%, 10.5%, 5.6%, 8.5%, and 9.7%, respectively. Risk factors associated with specific antibodies against HLA-A, -B, -C, -DP, -DQ, and -DR were female gender, prior transfusion, previous pregnancy, and underlying disease. Our findings suggest that gender, prior pregnancy, transfusion and underlying diseases are risk factors for HLA sensitization, which could guide HLA antibody monitor and donor selection.

Utility of flexible bronchoscopy with polymerase chain reaction in the diagnosis and management of pulmonary infiltrates in allogeneic HSCT patients

Pulmonary infiltrates in allogeneic hematopoietic stem cell transplant (allo‐HSCT) patients are potentially life‐threatening and require early diagnosis and treatment. We aimed to retrospectively explore the clinical efficacy of polymerase chain reaction (PCR) in conjunction with flexible bronchoscopy (FB) in allo‐HSCT patients with pulmonary infiltrates.