Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRDnegative group(MRD‒_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD‒_CD8 clusters and vice versa.MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD‒_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.

Comparison of clinical features of nephrotic syndrome after haploidentical and matched donor hematopoietic stem cell transplantation

To the Editor:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is one of the most effective options for hematological diseases.However,allo-HSCT treatment can cause serious complications.Post-transplant kidney damage is an important complication.In this study,we retrospectively analyzed the frequency of nephrotic syndrome(NS)after allo-HSCT and compared the frequency and clinical characteristics of NS between haploidentical donor(HID)and matched donor(MD)HSCT(including matched sibling donors[MSD]and unrelated donors[URD]).

异基因造血干细胞移植后腺病毒感染的临床特征分析

目的分析异基因造血干细胞移植(allo-HSCT)后人腺病毒(HAdV)感染患者的临床特征及预后。方法回顾性病例系列研究。收集2015年8月至2019年10月在北京大学人民医院血液科接受allo-HSCT后出现疑似感染症状但感染病原不明的2728例患者标本,采用荧光定量PCR法检测HAdV DNA,HAdV DNA检测阳性视为HAdV感染。分析HAdV感染患者临床表现,并根据患者年龄、移植类型、移植年份、随访时间采用巢式病例配对按1∶3匹配了未发生HAdV感染的患者作为对照组,采用Kaplan-Meier法分析并进行Log-rank检验,比较HAdV感染组和对照组的临床预后。结果共检测7119份标本,其中36例患者99例次HAdV DNA阳性。36例HAdV感染患者中22例发生HAdV血症;24例除HAdV感染外合并1种或多种其他病毒感染;19例(53%)有发热,25例(69%)有消化道症状,11例(31%)有呼吸道症状,9例(25%)有肝功能异常,6例(17%)有神经系统症状;23例同时发生2度及以上急性移植物抗宿主病;9例患者接受西多福韦抗病毒治疗,其中7例HAdV转阴,2例治疗无效。所有患者随访时间[M(Q_(1),Q_(3))]为496(216,940)d,Kaplan-Meier分析显示HAdV感染组5年总体生存率低于对照组(48.4%±9.2%比91.3%±3.5%;χ^(2)=65.03,P<0.001),移植后5年的非复发死亡率高于对照组(40.8%±8.8%比4.0%±2.0%;χ^(2)=34.17,P<0.001)。结论allo-HSCT后HAdV感染者以消化道、呼吸道症状为主,合并2度以上急性移植物抗宿主病的风险增加,HAdV感染患者总体生存差,非复发死亡率高。

Comparison analysis between haplo identical stem cell transplantation and matched sibling donor stem cell transplantation for high-risk acute myeloid leukemia in first complete remission

In order to compare the effect between haploidentical(HID) stem cell transplantation(HSCT) and matched sibling donor(MSD)stem cell transplantation for high-risk acute myeloid leukemia(AML) in first complete remission status(CR1), we retrospectively studied 170 cases who received stem cell transplantation from Jan 2008 to Jul 2015 in Peking University People's Hospital. We divided all cases into MSD group(43 cases) and HID(127 cases) group. Patients in HID and MSD group displayed similar baseline characteristics except for age distribution. There were no statistic differences for overall survival(OS), cumulative incidence of relapse, leukemia free survival(LFS), transplantation related mortality(TRM) between HID and MSD group. The 3-year OS, LFS for all patients was 63.9% and 59.7% respectively. Multivariate analysis showed that grade III-IV acute graft versus host disease(aGVHD) was an independent risk factor for treatment related mortality(HR=8.134, 95% CI:3.210–20.611, P<0.001), monosomy/complex chromosomal karyotype and white blood cell count more than 50×109 L-1 were two independent factors for relapse(HR=1.533, 95% CI: 1.040–2.260, P=0.031)(HR=1.004, 95% CI: 1.001–1.008, P=0.015).Grade III-IV aGVHD was an independent factor for mortality(HR=3.184, 95% CI: 1.718–5.902, P<0.001). These results demonstrated some risk factors for high-risk AML leukemia transplantation and indicated for AML patients in CR1 status, haplo stem cell transplantation could have the same therapeutic effect as MSD transplantation.

Comparison of efficacy between HLA6/6-and HLA3/6-matched haploidentical hematopoietic stem cell transplant in T-cell-replete transplants between parents and children

To compare the efficacy of HLA6/6-matched haploidentical hematopoietic stem cell transplant(haplo-HSCT) with that of HLA3/6-matched HSCT in T-cell-replete transplants, we recruited 27 consecutive recipients from multiple centers who received HLA6/6-matched haplo-HSCT from a parent or child donor between February 2010 and May 2016. A matched-pair analysis was designed. For each recipient from the study cohort, two recipients were randomly selected from the control cohort and matched(according to patient age, patient sex, disease type, disease status, donor age, donor sex, and recipient-donor relationship). No significant differences were found in hematopoietic recovery. The incidence of grade II–IV and III–IV acute graft versus host disease was similar(18.5% vs. 31.5%, P=0.216; 11.1% vs. 9.3%, P=0.792) in the HLA6/6 and HLA3/6 groups, respectively. The3-year cumulative incidence of relapse was 14.8% and 17.0%(P=0.800). The 3-year cumulative incidence of nonrelapse mortality was 12.1% and 17.6%(P=0.751). The estimated 3-year disease-free survival was 73.1% and 65.5%(P=0.489). The estimated 3-year overall survival was 74.7% and 74.0%(P=0.946). The data suggested the efficacy and safety of the HLA6/6-and the HLA3/6-matched haplo-HSCT between parents and children are comparable. That HLA-mismatch disparity is not correlated with T-cell-replete haplo-HSCT outcome was substantiated.

Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation

The efficacy of salvage interferon-α(IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI)(n=24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.

Comparison of the clinical outcomes of hematologic malignancies after myeloablative haploidentical transplantation with G-CSF/ATG and posttransplant cyclophosphamide:results from the Chinese Bone Marrow Transplantation Registry Group(CBMTRG)

This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation(haploHSCT)for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group(CBMTRG).For each PTCy,G-CSF/ATG subjects(1:4)were selected using the nested case-pair method.In total,220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed.The incidences of 30-day neutrophil engraftment(88.6%vs.96.6%,P=0.001),90-day platelet engraftment(84.1%vs.94.2%,P=0.04),the median time to neutrophil engraftment(17 days vs.12 days,P=0.000)and platelet engraftment(22 days vs.17 days,P=0.001)were significantly inferior in PTCy group.The incidences of grades 2–4 and 3–4 acute graft-versus-host disease(GVHD),chronic GVHD and severe chronic GVHD were comparable.Among G-CSF/ATG and PTCy groups,the 3-year progression-free survival,overall survival,cumulative incidences of nonrelapse mortality and relapse was 74.3%vs.61%(P=0.045),78.3%vs.65.2%(P=0.039),12%vs.27.3%(P=0.008),and 14.9%vs.11.7%(P=0.61),respectively.G-CSF/ATG can achieve better engraftment,PFS and OS,and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.

Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism

The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis Brelated compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group(n=29), a prednisone group(n=25), a levothyroxine group(n=32) and a prednisone plus levothyroxine group(n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients(29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.

Improved clinical outcomes of rhG-CSF-mobilized blood and marrow haploidentical transplantation compared to propensity score-matched rhG-CSF-primed peripheral blood stem cell haploidentical transplantation:a multicenter study

The effects of haploidentical rhG-CSF-mobilized blood and marrow transplantation(HBMT) on hematological malignances are well established. Previous prospective single-center studies have demonstrated better survival after HBMT versus haploidentical rhG-CSF-mobilized peripheral blood stem cell transplantation(HPBSCT) for acute leukemia(AL) not in remission(NR) or in more than the second complete remission(>CR2). To test the hypothesis that HBMT is still superior to HPBSCT for patients with AL, multiple myeloma(MM), or non-Hodgkin lymphoma(NHL) in CR1/CR2 and for patients with chronic myeloid leukemia in the first and second chronic phase lacking a matched donor, we designed a propensity score method-based multicenter study.Hematopoietic recovery, acute graft-versus-host disease(aGVHD), and chronic GVHD were comparable between the HBMT group(n=168) and the HPBSCT group(n=42). No significant differences were found in non-relapse mortality rate(20.17%±3.58%and 27.24%±7.16%, P=0.18) or relapse rate(19.96%±3.72% and 28.49%±8.25%, P=0.32) between the HBMT group and the HPBSCT group. HBMT recipients had better overall survival(65.0%±4.2% and 54.2%±8.3%, P=0.037) and disease-free survival(59.9%±4.6% and 44.3%±8.7%, P=0.051). Multivariate analysis showed that HPBSCT was associated with poorer DFS(HR(95%CI), 1.639(0.995–2.699), P=0.052). Our comparisons showed that HBMT was superior to HPBSCT as a post-remission treatment for patients lacking an identical donor.

Reduced β2-GPI is associated with increased platelet aggregation and activation in patients with prolonged isolated thrombocytopenia after allo-HSCT

We aimed to measure platelet function and its relationship with β2-GPI in prolonged isolated thrombocytopenia(PT) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Fifty-six patients with PT and 60 allo-HSCT recipients without PT(non-PT controls) were enrolled.Platelet aggregation and activation,β2-GPI and anti-β2-GPI antibody levels,vWF antigen,and vWF activity were analyzed.The effect of β2-GPI on platelet aggregation was also measured ex vivo.Results showed that ADP-induced platelet aggregation significantly increased(39%±7.5% vs.23%±8.5%,P=0.032),and the platelet expression of both CD62 p(33.6%±11.6% vs.8.5%±3.5%,P<0.001) and PAC-1(42.4%±7.6% vs.6.8%±2.2%,P<0.001) was significantly higher in patients with PT than in those without PT.Significantly lower β2-GPI levels(164.2±12 μg m L^-1 vs.234.2±16 μg mL^-1,P<0.001),higher anti-β2-GPI IgG levels(1.78±0.46 U mL^-1 vs.0.94±0.39 U mL^-1,P<0.001),and increased vWF activity(133.06%±30.50% vs.102.17%±25.90%,P<0.001) were observed in patients with PT than in those without PT.Both ADPinduced platelet aggregation(n=116,r^2=-0.5042,P<0.001) and vWF activity(n=116,r^2=-0.2872,P<0.001) were negatively correlated with β2-GPI levels.In summary,our data suggested that platelet aggregation and activation were significantly higher in patients with PT than in those without PT,which might be associated with reduced β2-GPI levels.The reduced β2-GPI levels might be due to the existence of anti-β2-GPI IgG.

Modification of donor lymphocyte infusion: how to improve the outcome?

(HSCT),which has been acknowledged as a curative procedure,relapse of leukemia remains the leading cause of death following transplantation and is a disappointment to transplant physicians.Leukemic relapse occurs due to leukemia cell escape from immune-mediated killing (immune escape) by pre-transplantation conditioning and post-transplantation immune control.Immune exhaustion of donor T cells is one of the common causes of relapse,and donor lymphocyte infusions (DLIs) have the potential to reverse this immune exhaustion.Patients who are deemed eligible for intensive treatment at this point are offered either DLI or a second transplant.Contrary to the contemporary understanding,DLI results in the same response and survival obtained via a second transplant but with less toxicity (Kharfan- Dabaja et al.,2018).Starting in the mid-1990s,our group along with few others demonstrated the efficacy of DLI,which was initially confirmed by the Hadassah group in Jerusalem in the late 1980s.In the first four patients (with both acute and chronic leukemias) treated by us with DLI,the initial success rate was 100%,which encouraged us to pursue this treatment further.

Arsenic trioxide alleviates acute graft-versus-host disease by modulating macrophage polarization

This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.

Minimal residual disease-directed immunotherapy for high-risk myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

The efficacy of minimal residual disease (MRD)-directed immunotherapy,including interferon-α (IFN-α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI),was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT).High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after ailo-HSCT were studied (n =47).The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample.The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P=0.377)and 9.1% and 0.0% (P=0.985) for patients in the IFN-α and chemo-DLI groups,respectively.The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P =0.891) and 84.3% and 84.6% (P=0.972) for patients in the IFN-α and chemo-DLI groups,respectively.Persistent MRD after immunotherapy was associated with poor survival.Thus,the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after alIo-HSCT,and the efficacy was comparable between chemo-DLI and IFN-α treatment.

Haploidentical hematopoietic cell transplantation for severe acquired aplastic anemia: a case-control study of post-transplant cyclophosphamide included regimen vs. anti-thymocyte globulin & colony-stimulating factor-based regimen

Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).

Risk factors for chronic graft-versus-host disease after anti-thymocyte globulin-based haploidentical hematopoietic stem cell transplantation in acute myeloid leukemia

Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from cGVHD.The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci mismatched.The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other donors.The patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without aGVHD.In multivariate analysis,grades III to IV aGVHD was the only independent risk factor for cGVHD.Thus,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes

Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9%vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001).The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%,respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions(P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.

Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed acute leukemia post-chemotherapy plus modified donor lymphocyte infusion

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation(allo-HSCT).The outcome of a second allo-HSCT(HSCT2)for relapse post-HSCT has shown promising results in some previous studies.However,little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia(AL)post-chemotherapy plus modified donor lymphocyte infusion(post-Chemo+m-DLI)after the first allo-HSCT(HSCT1).Therefore,we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo+m-DLI in our center.With a median follow-up of 918(457–1732)days,26 patients(92.9%)achieved complete remission,and 2 patients exhibited persistent disease.The probabilities of overall survival(OS)and disease-free survival(DFS)1 year after HSCT2 were 25.0%and 21.4%,respectively.The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1%±4.9%and 25.0%±8.4%.The cumulative incidences of relapse were 50.0%±9.8%and 53.5%±9.9%at 1 and 2 years post-HSCT2,respectively.Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2,and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2.Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo+m-DLI.

Bridging chimeric antigen receptor T-cell before transplantation improves prognosis of relapsed/refractory B-cell acute lymphoblastic leukemia

To the Editor:For recipients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),allogeneic hematopoietic stem cell transplantation(allo-HSCT)often fails to provide them with a satisfactory prognosis.The chimeric antigen receptor T(CAR-T)cells are proven to be safe and effective for these patients.[1]But there are few published studies assessing the advantages of CAR-T compared to traditional chemotherapy as a bridging treatment followed by HSCT.Consequently,we conducted this study to confirm whether children and young adult R/R B-ALL patients with CAR-T therapy could expect a better post-HSCT prognosis,compared to R/R patients only receiving traditional chemotherapy before transplantation.