Revisiting cytomegalovirus serology in allogeneic hematopoietic cell transplant recipients

Background: Allogeneic hematopoietic cell transplant recipients (allo-HCTR) with positive CMV serology may have false positive results due to blood product transfusions associated passive immunity. Methods: This is a single-center cohort study including consecutive adult allo-HCTR (01.01.2018-31.12.2022) with negative baseline (at hematologic malignancy diagnosis) and indeterminate or low-positive (CMV-IgG-titer: ≥ 0.6-&lt;50 U/mL) pretransplant CMV-serology with negative pretransplant plasma CMV DNAemia. The CMV serology status of those patients was reclassified from R + to R- (CMVR- reclassification group). We compared those patients to allo-HCTR with negative (CMV-IgG-titer &lt; 0.6 U/mL) pretransplant CMV IgG serology (CMVR- group). We describe the number and type of patients, whose pretransplant CMV serology status was reclassified from indeterminate/positive to negative. Moreover, we reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups, to assess the safety of this approach. Results: Amongst 246 (84.5%) of 291 transplanted patients identified as CMVR + pretransplant, 60/246 (24.4%) were reclassified from CMV serology indeterminate (N:10) or low-positive (N:50) to R-. Only 1/60 (1.67%) patient in the CMVR- reclassification group vs 3/44(6.8%; p = 0.30) in the CMVR- group developed CMV-DNAemia during the 6-month posttransplant follow-up period. There were no significant differences in the number of CMV-DNAemia tests performed, CMV-DNAemia range and time posttransplant between the two groups. Conclusion: One out of four allo-HCT CMVR + may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV-serology testing at hematologic malignancy diagnosis in allo-HCTR candidates and careful review of pretransplant CMV IgG-titers may help correctly classify CMV-serology status.</p

Evaluation of Disease Risk Comorbidity Index after Allogeneic Stem Cell Transplantation in a Cohort with Patients Undergoing Transplantation with In Vitro Partially T Cell Depleted Grafts

Outcomes of hematopoietic stem cell transplantation (HSCT) are influenced by comorbidities, disease type, and status at transplantation. Several prognostic scores can be used, such as the disease risk index (DRI) or the hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Recently, a new prognostic tool, the disease risk comorbidity index (DRCI), combining the DRI and the HCT-CI, was published. The DRCI determines 6 patient groups (very low risk [VLR], low risk [LR], intermediate risk 1 [IR-1], intermediate risk 2 [IR-2], high risk [HR], and very high risk [VHR]) with a significant predictive value for overall survival (OS), disease-free survival (DFS), relapse incidence (RI), and graft-versus-host disease-free/relapse-free survival (GRFS). However, the DRCI has not been evaluated for patients allografted with partially in vitro T cell depleted (pTDEP) grafts. In our center, we offer pTDEP to reduce graft-versus-host disease for patients in complete remission at transplant time. In this retrospective study, we investigated the DRCI in 404 adult patients (including 37.6% pTDEP) undergoing a first HSCT for hematological malignancies from 2008 to 2018. Because of the small number of patients in LR, VLR and LR were combined for analysis. In the entire cohort, 2-year OS was 84.4% (95% CI, 71.6% to 97.2%) for LR, 61.6% (54.8% to 68.4%) for IR-1, 45.7% (33.3% to 58.1%) for IR-2, 31% (19.4% to 42.6%) for HR, and 30.9% (14.5% to 47.3%) for VHR (P < .001). In addition, the DRCI was predictive of DFS, RI, and GRFS but not of nonrelapsed mortality and graft-versus-host disease. Our study confirms similar results with the original publication but gives less accurate prognosis information than the DRI and HCT-CI when used separately. In conclusion, the DRCI does not seem to offer more relevant information than the DRI and HCT-CI to help physicians and patients for the HSCT decision

Defibrotide Shows Efficacy in the Prevention of Sinusoidal Obstruction Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation : A Retrospective Study

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a well-known complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with a mortality rate of up to 85%. Defibrotide has shown efficacy in treatment of SOS/VOD. Moreover, evidence exists supporting the efficacy of defibrotide as SOS/VOD prophylaxis. We have previously reported our single center experience on 52 HSCT recipients receiving defibrotide as SOS/VOD prophylaxis, which has shown that the patients did not develop any SOS/VOD under this prophylaxis. The aim of the present study was to see if we can confirm the previous results, mainly on the decrease incidence of SOS/VOD, as well as improve event-free survival (EFS) on a larger study population. We extended our previous study in a single-center retrospective analysis to include 237 consecutive patients (248 transplantations) who underwent transplantation between 1999 and 2009 for hematological diseases and receiving intravenous defibrotide as prophylaxis. This cohort was compared to 241 patients (248 transplantations) treated before 1999 or after 2009 when defibrotide prophylaxis was not routinely used in our center. Median follow-up for the study group was 10 (range 2-16) years and for the control group 2.7 (range 1-18) years. None of the 237 patients in the defibrotide group developed SOS/VOD. The cumulative incidence (CI) of SOS/VOD was 0% in the defibrotide group as compared to 4.8% (95% confidence interval [CI], 2.6-8%; P= .00046) in the control group. There was also a better 1-year EFS with 38% (95% CI, 32%-44%) in the defibrotide group versus 28% (95% CI, 22%-34%) (P= .00969) and decreased cumulative incidence of acute graft-versus-host disease (GvHD) in the defibrotide group 31% (95% CI, 25%-37%) versus 42% (95% CI, 36%-48%) (P= .026). The 1-year overall survival, relapse incidence, and non-relapse mortality were not statistically different. Multivariable analysis, performed taking into account clinical factors known to influence the risk of SOS/VOD, confirmed the favorable impact of defibrotide on SOS/VOD (HR 1.38e-08 [95% CI, 3.28e-09-5.80e-08]; P&lt; .00001). Conversely, multivariable analysis failed to confirm the impact of defibrotide on 1-year EFS or acute GvHD. This large retrospective study on SOS/VOD-prophylaxis with defibrotide suggests that this approach may be of benefit. These results need to be confirmed in a prospective randomized trial