The post-transplant scoring system (PTSS) is associated with outcomes in patients with MDS after CD34+selected allogeneic stem cell transplant.

The post-transplant scoring system (PTSS), developed by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, is based on three independent post-transplant risk factors: grade of acute graft-versus-host disease, lack of platelet recovery before day 100, and relapse before day 100; discriminating low- (0), intermediate- (1-3), and high-risk (4-8) patients. We investigated the prognostic value of the PTSS in a cohort of patients with MDS who underwent myeloablative CD34-selected TCD transplants. From 2008 to 2018, 109 patients underwent a first TCD-HCT for MDS at our center. We used Cox proportional hazards models and different landmark analyses to evaluate the association of categorized PTSS score risk groups with overall survival (OS). Patients with an intermediate/ high risk PTSS score had decreased OS at day 180 (univariate HR 3.25 [95% CI 1.60, 6.60], p = 0.001) and at day 365 (univariate HR 5.42 [95% CI 2.21, 13.3], p < 0.001) compared to low risk PTSS scores. This association remained significant after adjusting for HCT-CI. PTSS score calculated at day 100 was not associated with OS, even after adjusting for HCT-CI subgroups. In summary, the PTSS predicted survival at day 180 and day 365 in recipients of T-cell-depleted allografts for myelodysplastic syndrome.

Cryopreservation of unrelated donor hematopoietic stem cells: the right answer for transplantations during the COVID-19 pandemic?

Cryopreservation was recommended to ensure continuity of unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) during COVID-19 pandemic. However, its impact on clinical outcomes and feasibility was not well known. We compared 32 patients who underwent UD HSCT using cryopreserved peripheral blood stem cells (PBSC) during the COVID-19 pandemic with 32 patients who underwent UD HSCT using fresh PBSC in the previous period. Median neutrophil engraftment was 17.5 and 17.0 days with cryopreserved and fresh grafts, respectively. Non-significant delays were found in platelet recovery days (25.5 versus 19.0; P = 0.192) and full donor chimerism days (35.0 and 31.5; P = 0.872) using cryopreserved PBSC. The rate of acute graft-versus-host disease at 100 days was 41% (95% CI [21-55%]) in cryopreserved group versus 31% (95% CI [13-46%]) in fresh group (P = 0.380). One-hundred days progression-relapse free survival and overall survival did not differ significantly. During COVID-19 pandemic, six frozen UD donations were not transfused and logistical and clinical issues regarding cryopreservation procedure, packaging, and transporting appeared. In summary, UD HSCT with cryopreserved PBSC was safe during this challenging time. More efforts are needed to ensure that all frozen grafts are transplanted and cryopreservation requirements are harmonized.

Utilidad del lavado broncoalveolar y la citometría de flujo en pacientes con hemopatías malignas e insuficiencia respiratoria / Usefulness of bronchoalveolar lavage and flow cytometry in patients with hematological malignancies and respiratory failure

Antecedentes y objetivo. Para mejorar la eficiencia del lavado broncoalveolar (LBA) son necesarias nuevas estrategias. Con esta finalidad se desarrolló un estudio para establecer el valor diagnóstico del LBA en pacientes con hemopatías malignas e infiltrados pulmonares. Pacientes y método. Se analizó la correlación del estudio citológico y la citometría de flujo del LBA con los hallazgos microbiológicos y la evolución clínica. Resultados. Se analizaron setenta LBA y se realizó estudio de citometría de flujo en 23 de ellos. Cincuenta y tres pacientes no presentaron ningún efecto adverso atribuible al LBA. Se modificó el tratamiento antiinfeccioso en 64 (un 91%) de los pacientes. La cifra de linfocitos T >0,3×109/l en sangre periférica se asoció a una mayor supervivencia global a los 3 años (el 53 vs. 22%, p=0,009). Una cifra más elevada de linfocitos T CD4 (>20/μL) y CD8 (>35/μL) en el LBA se asoció a una mayor supervivencia global a los 3 años: el 82 vs. 21% (p=0,030) y el 80 vs. 23% (p=0,059). Conclusiones. Nuestro estudio confirma el valor clínico del LBA en la estrategia terapéutica de pacientes con hemopatías malignas e insuficiencia respiratoria (AU)

Background and objectives. Strategies to improve the efficiency of bronchoalveolar lavage (BAL) are needed. We conducted a study to establish the diagnostic value of BAL in patients with hematological malignancies and pulmonary infiltrates. Patients and methods. The correlation of cytologic and flow cytometric study of BAL with the microbiological findings and the clinical evolution was determined. Results. Seventy BAL were performed and flow cytometric study was analyzed in 23 of them. Fifty-three patients did not present any adverse event attributable to BAL. Anti-infectious therapy was modified in 64 (91%) patients. T lymphocyte count >0.3×109/l in peripheral blood was associated with longer OS at 3 years (53 vs. 22%, p=.009). Higher CD4 (>20/μL) and CD8 (>35/μL) lymphocyte counts in the BAL were associated with a longer OS at 3 years: 82 vs. 21% (p=.030) and 80 vs. 23% (p=.059). Conclusions. Our study confirms the clinical value of BAL for treatment decision making in patients with hematological malignancies and acute respiratory failure (AU)

Usefulness of bronchoalveolar lavage and flow cytometry in patients with hematological malignancies and respiratory failure. / Utilidad del lavado broncoalveolar y la citometría de flujo en pacientes con hemopatías malignas e insuficiencia respiratoria.

BACKGROUND AND OBJECTIVES: Strategies to improve the efficiency of bronchoalveolar lavage (BAL) are needed. We conducted a study to establish the diagnostic value of BAL in patients with hematological malignancies and pulmonary infiltrates. PATIENTS AND METHODS: The correlation of cytologic and flow cytometric study of BAL with the microbiological findings and the clinical evolution was determined. RESULTS: Seventy BAL were performed and flow cytometric study was analyzed in 23 of them. Fifty-three patients did not present any adverse event attributable to BAL. Anti-infectious therapy was modified in 64 (91%) patients. T lymphocyte count >0.3×109/l in peripheral blood was associated with longer OS at 3 years (53 vs. 22%, p=.009). Higher CD4 (>20/µL) and CD8 (>35/µL) lymphocyte counts in the BAL were associated with a longer OS at 3 years: 82 vs. 21% (p=.030) and 80 vs. 23% (p=.059). CONCLUSIONS: Our study confirms the clinical value of BAL for treatment decision making in patients with hematological malignancies and acute respiratory failure.

Early and Long-Term Impaired T Lymphocyte Immune Reconstitution after Cord Blood Transplantation with Antithymocyte Globulin.

Immune reconstitution is crucial to the success of allogeneic hematopoietic stem cell transplantation. Umbilical cord blood transplantation (UCBT) has been associated with delayed immune reconstitution. We characterized the kinetics and investigated the risk variables affecting recovery of the main lymphocyte subsets in 225 consecutive pediatric and adult patients (males, n = 126; median age, 15; range, .3 to 60; interquartile range, 4 to 35) who underwent myeloablative single UCBT between 2005 and 2015 for malignant and nonmalignant disorders. Low CD4+ and CD8+ T cell counts were observed up to 12 months after UCBT. In contrast, B and natural killer cells recovered rapidly early after transplantation. In a multivariate regression model, factors favoring CD4+ T cell recovery ≥ 200 cells/µL were lower dose antithymocyte globulin (ATG) (hazard ratio [HR], 3.93; 95% confidence interval [CI], 2.3 to 5.83; P = .001), negative recipient cytomegalovirus (CMV) serostatus (HR, 3.76; 95% CI, 1.9 to 5.74; P = .001), and younger age (HR, 2.61; 95% CI, 1.01 to 3.47; P = .03). Factors favoring CD8+ T cell recovery ≥ 200 cells/µL were lower dose ATG (HR, 3.03; 95% CI, 1.4 to 5.1; P = .03) and negative recipient CMV serostatus (HR, 1.9; 95% CI, 1.63 to 2.15; P = .01). Our results demonstrate the significant negative impact of ATG on lymphocyte recovery. A reduction of the dose or omission of ATG could improve immune reconstitution and perhaps reduce opportunistic infections after UCBT.

Cord Blood Units with High CD3(+) Cell Counts Predict Early Lymphocyte Recovery After In Vivo T Cell-Depleted Single Cord Blood Transplantation.

Although high absolute lymphocyte count (ALC) early after transplantation is a simple surrogate for immune reconstitution, few studies to date have established the predictive factors for ALC after umbilical cord blood transplantation (UCBT). We retrospectively studied the factors associated with early lymphocyte recovery and the impact of the ALC on day +42 (ALC42) of ≥300 × 10(6)/L on outcomes in 210 consecutive pediatric and adult patients (112 males; median age, 15 years; range, 0.3 to 60 years; interquartile range, 4 to 36 years) who underwent myeloablative in vivo T cell-depleted single UCBT between 2005 and 2014 for malignant and nonmalignant disorders. In a logistic multivariate regression model, factors favoring a higher ALC42 were higher infused CD3(+) cell dose (odds ratio [OR], 2.7; 95% CI, 1.4 to 5.2; P = .004), lower antithymocyte globulin dose (OR, 2.3; 95% CI, 1.2 to 4.5; P = .01), and better HLA match (OR, 2.1; 95% CI, 1.1 to 4.1; P = .03). In multivariate analysis, lower ALC42 was associated with higher nonrelapse mortality (hazard ratio [HR], 1.76; 95% CI, 1.34 to 2.32; P = .001), whereas a higher ALC42 was associated with better disease-free survival (HR, 2.03; 95% CI, 1.15 to 3.6; P < .001) and overall survival (HR, 2.03; 95% CI, 1.17 to 3.6; P < .001). Our study suggests that the selection of better HLA-matched cord blood units containing higher CD3(+) cell counts and the use of conditioning regimens with lower ATG doses could improve immune reconstitution after UCBT.

Post-Thaw Viable CD45+ Cells and Clonogenic Efficiency are Associated with Better Engraftment and Outcomes after Single Cord Blood Transplantation in Adult Patients with Malignant Diseases.

The quantity of cells is widely accepted as the main factor influencing the outcome after umbilical cord blood transplantation (UCBT) however, the quality of the cord blood units (CBUs) has been less studied. In order to determine the impact of qualitative variables in UCBT outcomes, we conducted a multicenter retrospective study in adult patients with hematological malignancies who underwent single UCBT after a common myeloablative conditioning regimen. One hundred and ten patients from 3 institutions [median age, 35 years (range 18-55)] were included. Quantitative (TNC and total CD34+cells) and qualitative variables [viable CD45+ (vCD45+), vCD34+ and clonogenic efficiency [(CLONE), quotient of post-thaw colony-forming units (CFU)] and pre-freeze CD34+ cells predicted engraftment in univariate analysis however, only 2 qualitative variables remained significant in the multivariate analysis. Infusion of more than 2 × 10(7) post-thaw vCD45+ cells per kilogram was significantly associated with faster neutrophil (P = .01), platelet engraftment (P = .01), higher disease-free (P = .01) and overall survival (0.02). In addition, CLONE ≥ 20% predicted a faster neutrophil (P = .005), platelet engraftment (P = .01) and contributed to decrease the non-relapse mortality (P = .02). Our study suggests that the vCD45+ cells dose and CLONE are powerful surrogate markers of graft quality and can potentially help on CBUs selection if tested with representative reference samples.

Few and nonsevere adverse infusion events using an automated method for diluting and washing before unrelated single cord blood transplantation.

Graft dilution and DMSO washing before cord blood (CB) administration using an automated system may offer low incidence of adverse infusion events (AIE), ensuring reproducible cell yields. Hence, we analyzed the incidences and significance of immediate AIE, cellular yield, and engraftment after single CB infusion. One hundred and fifty-seven patients (median age, 20 years; range, 1 to 60) received a single CB unit for treatment of hematologic and nonhematologic malignancies with myeloablative conditioning after graft dilution and washing. The median total nucleated cell (TNC) doses was 3.4 × 10(7)/kg (range, 2 to 26) and the median post-thaw recovery was 84% (range, 45 to 178). The cumulative incidence of neutrophil engraftment at 50 days was 84% (95% confidence interval [CI], 83 to 93). A total of 118 immediate AIE were observed in fifty-two (33%) patients. All reported AIE were transient, graded from 1 to 2 by Common Terminology Adverse Events version 4. The most frequent toxicity was cardiovascular but without any life-threatening reaction. Infused TNC, recipient's weight, and rate of infusion per kilogram were risk factors associated with cardiovascular AIE in multivariate analysis (odds ratio [OR], 1.2 (95% CI, 1.1 to 1.4); P < .001; OR, .94 (95% CI, .9 to .97); P < .001; and OR, 1.5 (95% CI, 1.2 to 1.8); P < .001; respectively). In summary, use of an automated method for graft washing before CB administration showed low incidence of AIE without compromising cell yields and engraftment. Infused TNC dose, recipient's weight, and rate of infusion per kilogram were risk factors associated with infusion reactions.

Combination of the Hematopoietic Cell Transplantation Comorbidity Index and the European Group for Blood and Marrow Transplantation score allows a better stratification of high-risk patients undergoing reduced-toxicity allogeneic hematopoietic cell transplantation.

This study was conducted to determine whether the integration of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score would improve individual capacity for stratification of high-risk HCT candidates. A total of 442 consecutive patients receiving an allogeneic HCT after reduced-toxicity conditioning was included. Final HCT-CI and EBMT scores were calculated and validated. Then, patients were grouped into a 6-category new combination model according to the HCT-CI (0, 1 to 2, ≥ 3) and EBMT scores (0 to 3, 4 to 7), and the model's predictive capacity was also evaluated. Median HCT-CI and EBMT scores were 3 and 4, respectively. Increased HCT-CI was associated with higher 4-year nonrelapse mortality (NRM) and lower 4-year overall survival (OS), whereas a high EBMT score was associated with higher 4-year NRM. The HCT-CI showed a trend for a better predictive capacity than the EBMT score (c-statistic .6 versus .54, P = .1). According to the new model, patients within HCT-CI of 0 and HCT-CI of 1 to 2 groups had similar risk of NRM independently of their EBMT score. Within the HCT-CI ≥ 3 group, patients with low EBMT score showed lower NRM (25% versus 40%, P = .04) and a trend to higher OS (52% versus 36%, P = .06) than patients with a high EBMT score. Moreover, patients with HCT-CI ≥ 3 and EBMT score 0 to 3 had similar outcomes than those with HCT-CI of 1 to 2. In conclusion, the combination of HCT-CI and the EBMT score is feasible and might contribute to a better identification of high-risk patients, improving selection of best allogeneic HCT candidates.

Hematopoietic stem cell transplantation in patients with lymphomatoid granulomatosis: a European group for blood and marrow transplantation report.

Lymphomatoid granulomatosis (LG) is a very rare, Epstein-Barr virus-associated lymphoproliferative disorder of B cells. Prognosis is poor, particularly after relapse and no curative treatment exists. We report the results of high-dose therapy and autologous stem cell transplantation (ASCT) or reduced-intensity conditioning and allogeneic stem cell transplantation (alloSCT) in patients with multiply relapsed LG. A European Group for Blood and Marrow Transplantation survey identified 10 patients who had received 9 ASCT and 4 alloSCT. All patients had active disease at the time of transplantation. With a median follow-up of 5.1 (range, 1.4 to 6.3) years, 6 patients are alive and disease-free. Two ASCT patients died of septicemia early after transplantation, and 1 committed suicide after being in continuous complete remission 19 months after ASCT. Another patient allografted 4 years after ASCT remained disease-free but died of severe graft-versus-host disease 3 months after alloSCT. High-dose therapy followed by ASCT and alloSCT are effective therapeutic options and should be considered in all patients with refractory and multiply relapsed LG.