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Objective: To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA). Methods: This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People's Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method. Results: In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n =11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n =26). Most patients ( n =28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions: Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Objective: To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF). Methods: In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People's Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed. Results: Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q 1 , Q 3 )] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion: Matched sibling allo-HSCT is a feasible option for the treatment of MF.

A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [ M ( Q 1 , Q 3 )] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P >0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P >0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P >0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

This is a report of three cases of three male patients. One of the patients had myelodysplastic syndrome, and two had aplastic anemia; their ages were 28, 32, and 21 years old, respectively. Two patients underwent sibling allogeneic hematopoietic stem cell transplantation, and one underwent haploidentical hematopoietic stem cell transplantation. All the patients showed elevated hemoglobin and hematocrit at 6, 16, and 9 months after transplantation, with normal white blood cells and platelets and no splenomegaly. All causes of secondary polycythemia were ruled out. Bone marrow morphology showed no erythroid hyperplasia. The PCR result for BCR-ABL (P210, P230, P190, and variants) was negative, and there were no mutations at the amino acid site 617 of JAK2, exon 12 of JAK2, exon 9 of CALR, and amino acid site 515 of MPL. All three patients had hypertension. One patient was treated with amlodipine, and the other two patients were treated with angiotensin receptor blockers. The durations of erythrocytosis for these three patients were 6 years and 3 months, 4 years and 7 months, and 5 years and 3 months, respectively through December 2022. There was no tendency for spontaneous remission. Erythrocytosis after hematopoietic stem cell transplantation is a rare complication. Previous reports in the literature suggest that the mechanism of post-transplant erythrocytosis in recipients of allogeneic hematopoietic stem cell transplantation may be different from that of recipients of other transplants.

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=- 4.28, P <0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P >0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ 2 =35.32, P <0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ 2 =9.23, P =0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment ( P =0.105), aGVHD ( P =0.348), and 100-day NRM ( P =0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Objective: To investigate the clinical characteristics and prognosis of human adenovirus (HAdV) infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This is a retrospective case series study. Patients who received allo-HSCT and had symptoms of HAdV infection were tested in the Hematology Department at Perking University People's Hospital from August 2015 to October 2019. Real-time quantitative PCR was used to detect HAdV DNA from 2 728 patients with potential infection. HAdV DNA-positive patients were defined as having HAdV infection. The clinical features of these patients were analyzed, and a case-pair method was used to select patients without HAdV infection as the control group in a 1∶3 ratio. The clinical results of the two groups were compared using Kaplan-Meier and Log-rank testing. Results: A total of 7 119 samples were tested for HAdV, of which 99 samples from 36 patients were positive. Of these patients, 22 developed HAdV viremia, and 24 patients had concurrent infection with another virus. Nineteen patients had fever (53%), 25 had gastrointestinal symptoms (69%), 11 had respiratory symptoms (31%), nine had reduced liver function (25%), and six had nervous system symptoms (17%). Twenty-three patients developed acute graft-versus-host disease of grade 2 or higher. Of all the patients with HAdV infection, nine were treated with cidofovir, seven of whom became HAdV negative and two had invalid treatment. The median follow-up time was 496 (216, 940) d post-HSCT. The overall survival at 5 years post HSCT was 48.4%±9.2% vs. 91.3%±3.5% ( χ 2 =65.03, P <0.001) in patients with and without HADV, respectively. The non-relapse mortality at 5 years post-HSCT was 40.8%±8.8% vs. 4.0%±2.0% ( χ 2 =34.17, P <0.001) in patients with and without HADV, respectively. Conclusions: After allo-HSCT, HAdV-infected patients are dominated by gastrointestinal and respiratory symptoms and have an increased risk of combined acute graft-versus-host disease of >2 degrees. Patients with HAdV infection have poor overall survival and high non-relapse mortality.

Objective: To investigate the application value of Metagenomic Next-Generation sequencing (mNGS) in infectious patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: Patients suspected with local or systemic infections were retrospectively included after allo-HSCT in our department from April 2019 to November 2020. Pathogenic microorganisms were tested by mNGS in samples from peripheral blood, cerebrospinal fluid, alveolar lavage Liquid, abscess, etc. Other diagnostic methods such as bacterial/fungal culture, viral PCR detection were simultaneously explored comparing with mNGS results. Results: A total of 112 samples in 83 patients were detected by mNGS, and 34 pathogenic microorganisms were determined. Among these positive samples, 11 strains of bacteria (17 times) with the most common Escherichia coli (4/17) were reported. There were 7 strains of fungi (10 times) detected with primary Candida albicans (7/29). Although arvovirus 30.2% (39/129) were predominantly detected, its diagnostic relevance with infections was not definite. Other pathogenic viruses including cytomegalovirus (CMV) 25.6% (33/129) and Epstein Barr virus (EBV) 14.0% (18/129)were of significance. Comparing with golden diagnostic criteria, the sensitivity of mNGS was 86.5%, and specificity was 45.0%. Regarding single pathogen infection, the consistency of mNGS and conventional methods was 82.9% (29/35), while it was 16/17 in combination infections. Conclusion: mNGS could be a potential method to determine pathogens in patients suspected with infections after allo-HSCT.

Objective: To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization. Methods: Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m 2 ) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results: There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n =46) experienced lower PHR (4.4% vs. 27.5%, P =0.003), and higher 3-year EFS (79.5% vs. 59.8%, P =0.020) compared to those with DSA MFI≥5 000 (group B, n =37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR ( HR =6.101, P =0.021). PHR was associated with higher NRM ( HR =4.110, P =0.026), lower DFS ( HR =3.656, P =0.019) and OS ( HR =3.656, P =0.019). Conclusion: Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.

Five patients with Fanconi anemia who received hematopoietic cell transplantation were retrospectively analyzed. The conditioning regimens included fludarabine, cyclophosphamide and anti-thymocyte globulin. Two patients received both bone marrow and peripheral blood stem cells as the source of stem cell grafts from haploidentical matched related donors, while the others received peripheral blood stem cells from unrelated donors. All patients tolerated well and reached hematopoietic reconstitution. One patient died of intracranial infection. During follow-up, 4 patients survived independent of transfusion with full donor chimerism.

Objective: To investigate the prognostic factors of late-onset severe pneumonia (LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From January 2009 to December 2015, 68 patients with LOSP after allo-HSCT at Peking University Institute of Hematology were enrolled. In this retrospective study, univariate and multivariate analysis were used to evaluate the prognostic factors for LOSP after allo-HSCT. Results: The median time from allo-HSCT to the development of LOSP was 213 (90-2 330) days. The overall survival rate was 42.6% (29/68). The median survival time from LOSP to death was 21 days. Early mortality was defined as death within 21 days after LOSP, as late death more than or equal to 21 days. The median oxygenation index was 199.15 (92.21-290.48) mmHg. LOSPs in thirty-two patients (36.8%) were caused by virus, bacteria, fungi or mixed pathogens. The median C-reactive protein (CRP) was 75.65 (0.94-451.00) mg/L. The median procalcitonin (PCT) was 0.66 (0.00-249.00) μg/L. The higher PCT value indicated an early higher mortality rate by the ROC curve (PCT: cut-off ≥0.94 μg/L). Furthermore, multivariate analysis suggested that PCT more than or equal to 0.94 μg/L was a risk factor for early death of LOSP ( OR =5.77, 95% CI 1.66-20.11, P =0.006). LOSP occurred later or equal to 213 days after allo-HSCT was also a risk factor of early death in LOSP ( OR =4.74, 95% CI 1.33-16.89, P =0.017). No previous history of chronic graft versus host disease (GVHD) ( OR =4.50, 95% CI 1.58-12.83, P =0.005) and LOSP later or equal to 213 days ( OR =4.40, 95% CI 1.61-11.99, P =0.004) were the risk factors of late death in LOSP. Conclusions: PCT more than or equal to 0.94 μg/L and LOSP later or equal to 213 days are the risk factors of early death in LOSP. No previous chronic GVHD and LOSP later or equal to 213 days are the risk factors of late death in LOSP.

Objective: To investigate the risk factors and prognosis of transplant-associated thrombotic microangiopathy (TA-TMA) following acute graft-versus-host disease (aGVHD), and to evaluate the factors that might influence the prognosis of TA-TMA., Methods: A nested case-control study was designed. Cases with TA-TMA (n = 33) and controls (n = 77) matched for age at allogeneic hematopoietic stem cell transplantation (allo-HSCT) and length of follow-up were identified from a cohort of 356 patients who suffered from aGVHD after allo-HSCT between 2009 and 2011., Results: The median time to presentation of TA-TMA was 3.5 (1.2-23.0) months post-HSCT. The median time from diagnosis and first-line treatment failure of aGVHD to TA-TMA diagnosis was 25 (7-257) days and 15 (5-257) days, respectively. aGVHD occurring beyond 60 days after allo-HSCT, initial grade III-IV aGVHD, first-line treatment failure and receiving tacrolimus as second-line treatment were independently associated with the occurrence of TA-TMA, and patients with two or more risk factors were at higher risk (OR = 210.0, P = 0.000). Twenty-two (66.7%) TA-TMA patients died. Progressive TA-TMA was the significantly adverse factor affecting the survival of TA-TMA cases. None of therapies could improve prognosis of patients with TA-TMA., Conclusion: Many characteristics of aGVHD were associated with TA-TMA, which help us to identify the individuals who are at higher risk of developing TA-TMA following aGVHD and to select the more reasonable GVHD therapeutic strategies.

Objective: To investigate the characteristics of liver enzyme between acute graft-versus-host disease (aGVHD) and non-aGVHD groups after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: The liver enzyme data of patients with or without aGVHD was analyzed., Results: Among the 371 patients, 158 developed aGVHD (41.6%) with a median time of 29.5 d. In non-aGVHD group, the median elevating times of ALT, AST, GGT, LDH were all ≤ 20 d after transplantation, which were significantly earlier than those of aGVHD group. The peak value of AST was much higher in aGVHD group, but the remaining liver enzyme showed no significant difference. In aGVHD group, the duration of AST, GGT and LDH was significantly longer than the non-occurrence of aGVHD group, but ALT and ALP showed no difference in duration. In ALT, AST, ALP and LDH elevating group, the occurrence rate of aGVHD was significantly higher, but only ALT and LDH elevation could enter logistic regression model. The sensitivity and veracity of ALT or LDH elevating only were not very good for the diagnosis of aGVHD, but if ALT and LDH both elevated after day 24 and persisted more than 22 d, the sensitivity and veracity were better., Conclusions: The change of liver enzyme is common in allo-HSCT and associates with the occurrence of aGVHD, and the liver enzyme elevating only may not be a good diagnostic index of aGVHD. If the dynamic characteristics of liver enzyme is taken into account and the effect of drug-induced liver injury could be excluded, the elevation of liver enzyme still have the diagnostic value of aGVHD.