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.

蓬莱9-1潜山储层岩性识别及油气富集特征

通过岩石薄片鉴定和岩石化学分析等手段,识别出蓬莱9-1油田潜山钻遇两套岩石组合。一是中新元古界中低级变质岩围岩,包括变质石英砂岩、石英岩、云母石英片岩等;二是花岗岩侵入体。花岗岩锆石LA-ICP-MS U-Pb定年结果显示,所测锆石206Pb/238U年龄集中于162~169 Ma,其加权平均年龄为165 Ma,该年代代表了花岗岩的形成时代,即该岩体于中侏罗世侵入到中新元古界地层。在岩矿鉴定和年代分析的基础上,通过各类岩性岩石物理特征研究,建立了该潜山带岩石的测井识别方法。分析了储层成因及控制因素,并提出了有利油气富集区带,为油气储量申报等奠定了基础。

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]).

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.

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.

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.

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.

Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell transplantation:PAH risk score

Skin and soft tissue infections(SSTIs)refer to infections involving the skin,subcutaneous tissue,fascia,and muscle.In transplant populations with hematological malignancies,an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly.However,to date,the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation(HSCT)patients remain unclear.This study included 228 patients(3.67%)who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital.The overall annual survival rate was 71.5%.We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure(PPGF),comorbidities of acute kidney injury(AKI),and hospital-acquired pneumonia(HAP)were independent risk factors for death in the study population.A PPGF-AKI-HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP.The areas under the curves of internal and external validation were 0.833(95%CI 0.760–0.906)and 0.826(95%CI 0.715–0.937),respectively.The calibration plot revealed the high consistency of the estimated risks,and decision curve analysis showed considerable net benefits for patients.

Influence of the degree of donor bone marrow hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation

This study evaluated the influence of the degree of donor bone marrow(BM)hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December 2017.Forty-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method(1:4).Primary graft failure including poor graft function and graft rejection did not occur in two groups.In BM hypoplasia and hyperplasia groups,the cumulative incidence(CI)of neutrophil engraftment at day 28(91.7%vs.93.8%,P=0.75),platelet engraftment at day 150(83.3%vs.93.8%,P=0.48),the median time to myeloid engraftment(14 days vs.14 days,P=0.85)and platelet engraftment(14 days vs.14 days,P=0.85)were comparable.The 3-year progression-free survival,overall survival,CI of non-relapse mortality and relapse were 67.8%vs.71.7%(P=0.98),69.8%vs.77.8%(P=0.69),18.5%vs.13.6%(P=0.66),and 10.2%vs.10.4%(P=0.82),respectively.In multivariate analysis,donor BM hypoplasia did not affect patient clinical outcomes after allo-HSCT.If patients have no other suitable donor,a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.

Is t(11;14)(q13;q32) good or bad for newly diagnosed multiple myeloma?

Cytogenetic aberrations(CAs)are vital markers for risk stratification of multiple myeloma(MM).The prognostic significance of the aberration,t(11;14)(q13;q32),in MM has remained controversial over recent years.In addition,studies on the heterogeneity of t(11;14)MM and the impact of additional CAs are rare.[1]We therefore conducted a retrospective study on relevant data collected at our center in order to further analyze the characteristics of Chinese patients with t(11;14)MM and elaborate on heterogeneity in their genetic profile.