Search

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.

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 dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People's Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test. Results: The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome. Conclusion: Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status 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.

Objective: Donor cytomegalovirus (CMV) serological negative status may have an adverse effect on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), while there is inadequate data for Chinese people. This study is to explore the impact of donor CMV serological status on the outcome of CMV seropositive patients receiving allo-HSCT. Methods: Our study retrospectively analyzed 16 CMV seropositive patients with hematological malignancies receiving allogeneic grafts from CMV seronegative donors (antibody IgG negative) at Peking University People's Hospital from March 2013 to March 2020, which was defined as D - /R + group. The other 64 CMV seropositive patients receiving grafts from CMV seropositive donors at the same period of time were selected as matched controls through a propensity score with 1∶4 depending on age, disease state and donor-recipient relationship (D + /R + group). Results: Patients in D - /R + group developed CMV DNAemia later than patients in the D + /R + group (+37 days vs. +31 days after allo-HSCT, P =0.011), but the duration of CMV DNAemia in D - /R + group was longer than that of D + /R + group (99 days vs. 34 days, P =0.012). The rate of CMV reactivation 4 times or more in D - /R + group was 4/16, significantly higher than that of D + /R + group (4.7%, 3/64, P =0.01). The incidences of refractory CMV DNAemia (14/16 vs. 56.3%, P =0.021) and CMV disease (4/16 vs. 4.7%, P =0.01) in D - /R + group were both higher than those in D + /R + group. In addition, the application of CMV-CTL as the second-line antiviral treatment in D - /R + group was more than that in D + /R + group. Univariate analysis and multivariate analysis suggested that CMV serological negativity is an independent risk factor for refractory CMV DNAemia and the duration of CMV infection. The cumulative incidence of aGVHDⅡ-Ⅳ, cGVHD, 3-year probability of NRM, overall survival, and the cumulative incidence of relapse were all comparable in two groups. Conclusions: Although there is no significant effect on OS and NRM, the incidence of refractory CMV DNAemia, the frequency of virus reactivation, and the development of CMV disease in D - /R + group are higher than those in controls. Therefore, CMV seropositive donors are preferred for CMV seropositive patients.

Objective: To investigate the threshold of cytomegalovirus (CMV) DNAemia for preemptive antiviral therapy in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Viral load between 1×10(3) copies/ml and 5×10(3) copies/ml was defined as low viral load by real time Q-PCR. Clinical data and outcome were collected. Results: A total of 95 allo-HSCT recipients with low viral load from September 2014 to February 2015 were recruited in this study. The control group included 37 patients who received preemptive initial antiviral therapy. The other 58 patients didn't received antiviral treatment after positive viremia was confirmed. During monitoring, CMV viremia was cleared spontaneously in 17 patients of study group. Among 41 patients with continuous positive viremia in study group, 26 patients received antiviral therapy after second positivity including 18 with viral load >5×10(3) copies/ml, 2 with fever but still low viral load, 2 with hemorrhagic cystitis and low viral load, 4 with continuous low viral load. Eleven patients received antiviral therapy after the third positivity including 5 with viral load >5×10(3) copies/ml, 1 low viral load patient with fever and diarrhea, 5 with continuous low viral load. Only 4 patients received antiviral therapy after the fourth positivity of >5×10(3) copies/ml. In the study group, 35 cases received ganciclovir and 6 cases received foscarnet. The incidence of neutropenia did not differ significantly between study and control groups [minimum of neutrophil count: (1.63±0.41)×10(9)/L vs. (1.58±0.36)×10(9)/L]. The proportion of viral load greater than 5×10(3) copies/ml in the first week was comparable in two groups. Successful viral clearance rate was not statistically different ( P =0.87). Of all 95 patients, no CMV diseases developed, neither did patient die of CMV infection. Conclusions: Spontaneous clearance of viremia occurs in some patients receiving allo-HSCT with low CMV viral load. Delayed antiviral treatment of continuous positive viremia does not prolong the whole treatment duration, neither contributes to the progression of CMV diseases.

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.