Frequency, Clinical Characteristics and Outcome of Adults With Acute Lymphoblastic Leukemia and COVID 19 Infection in the First vs. Second Pandemic Wave in Spain.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 infection has bimodal distribution in Europe with a first wave in March to June 2020 and a second in September 2020 to February 2021. We compared the frequency, clinical characteristics and outcomes of adults with acute lymphoblastic leukemia (ALL) and infection in the first vs. second pandemic waves in Spain. PATIENTS AND METHODS: In this prospective study the characteristics of ALL and COVID-19 infection, comorbidities, treatment and outcome in the two periods were compared. The study ended when vaccination against SARS-CoV-2 was implemented in Spain. RESULTS: Twenty eight patients were collected in the first wave and 24 in the second. The median age was 46.5 years (range 20-83). Patients from the first wave had a trend to more severe ALL (higher frequency of patients under induction or submitted to transplantation or under immunosuppressive therapy). No significant differences were observed in need for oxygen support, intensive care unit (ICU) requirement, days in ICU and time to COVID-19 infection recovery. Seventeen patients (33%) died, with death attributed to COVID infection in 15 (29%), without significant differences in the 100 day overall survival (OS) probabilities in the two waves (68% ± 17% vs. 56% ± 30%). The only prognostic factor for OS identified by was the presence of comorbidities at COVID-19 infection (HR: 5.358 [95% CI: 1.875- 15.313]). CONCLUSION: The frequency and mortality of COVID-19 infection were high in adults with ALL, without changes over time, providing evidence in favor of vaccination priority for these patients.

Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis: Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model.

Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P < .001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P < .001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF.

The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: There is a lack of studies comparing clinical outcomes among retrospective versus prospective cohorts of allogeneic stem cell transplant (allo-HCT) recipients with community acquired respiratory virus (CARV) infections. METHODS: We compare outcomes in two consecutive cohorts of allo-HCT recipients with CARV infections. The retrospective cohort included 63 allo-HCT recipients with 108 CARV infections from January 2013 to April 2016 who were screened and managed following standard clinical practice based on influenza and respiratory syncytial virus rapid antigen detection methods. The prospective cohort was comprised of 144 consecutive recipients with 297 CARV episodes included in a prospective interventional clinical surveillance program (ProClinCarvSur-P) based on syndromic multiplex PCR as first-line test from May 2016 to December 2018 at a single transplant center. RESULTS: CARV infections in the retrospective cohort showed more severe clinical features at the time of diagnosis compared to the prospective cohort (fever 83% vs. 57%, hospital admission 69% vs. 28% and lower respiratory tract 58% vs. 31%, respectively, p ≤ 0.002 for all comparisons). Antiviral therapy was more commonly prescribed in the prospective cohort (69 vs. 43 treated CARV episodes), particularly at the upper respiratory tract disease stage (34 vs. 12 treated CARV episodes). Three-month all-cause mortality was significantly higher in the retrospective cohort (n = 23, 37% vs. n = 10, 7%, p < 0.0001). Multivariate logistic regression analysis showed that recipients included in ProClinCarvSur-P had lower mortality rate [odds ratio 0.31, 95% confidence interval 0.12-0.7, p = 0.01]. CONCLUSION: This study report on outcome differences when reporting retrospective vs. prospective CARV infections after allo-HCT. Recipients included in a ProClinCarvSur-P had lower mortality.

Cytomegalovirus (CMV) infection and risk of mortality in allogeneic hematopoietic stem cell transplantation (Allo-HSCT): A systematic review, meta-analysis, and meta-regression analysis.

Controversy surrounds the potential association between cytomegalovirus (CMV) infection and increased risk of mortality after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). A systematic literature search was conducted using the PubMed, EMBASE, and Web of Science databases, assessing the association between CMV infection, as documented by the pp65 antigenemia assay or by polymerase chain reaction (PCR) using blood specimens, and overall mortality (OM) and nonrelapse mortality (NRM) in the allo-HSCT setting. Pooled effects were estimated using the generic inverse variance random effects model. Heterogeneity was evaluated by Cochrane's Q test and I2 statistics. The source of heterogeneity was investigated by meta-regression and subgroup analyses. Twenty-six of 1367 studies fulfilled eligibility criteria. CMV infection identified by PCR monitoring was significantly associated with an increased risk of OM and NRM (hazard ratio 1.47, 95% confidence interval [1.20-1.81], P ≤ .001; hazard ratio 1.68, 95% confidence interval [1.14-2.49], P = .05, respectively). In this setting, the use of preemptive antiviral therapy (PET) resulted in a twofold increased risk of OM and NRM. The estimated effect sizes were associated with allo-HSCT modalities. Although our analyses point to an association between CMV infection and an increased risk of OM and NRM in allo-HSCT recipients, the high heterogeneity across studies prevented drawing of robust conclusions on this matter.

Results of compassionate therapy with intrathecal depot liposomal cytarabine in acute myeloid leukemia meningeosis.

Intrathecal (IT) depot liposomal cytarabine is useful in solid tumors or lymphomatous meningitis, but has scarcely been used in central nervous system (CNS) involvement in acute leukemia. We report the results of compassionate therapy with IT depot liposomal cytarabine in 10 patients with acute myeloid leukemia with CNS involvement. Five of 6 cases receiving this drug as the only IT therapy and the remaining 4 receiving it as adjuvant therapy to other CNS-directed therapies showed clearance of cerebrospinal fluid blast cells, with sustained response in 5 and mild side effects. Systemic therapy was given concomitantly in all cases, with high-dose cytarabine in 6. Clinical trials should establish the role of IT liposomal cytarabine in leukemic meningitis.