Poor graft function after haploidentical stem cell transplantation with post-transplant cyclophosphamide.

This is a retrospective cohort study of consecutive adult patients who received a haploidentical-SCT (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a single centre. Poor graft function (PGF) was defined as the occurrence of either persistent neutropenia (ANC < 0.5 × 109/µL) with poor response to granulocyte colony-stimulating factors (G-CSF) and/or thrombocytopenia (platelets < 20 × 109/L) with transfusion dependence, with complete donor chimerism and without concurrent severe GVHD or underlying disease relapse, during the first 12 months after transplantation. Forty-four (27.5%) out of 161 patients were diagnosed with PGF. Previous CMV reactivation was significantly more frequent in patients with PGF (88.6% versus 73.5%, p = 0.04) and the number of reactivations was also higher in these patients. Besides, early CMV reactivations in the first 6 months post-SCT were also significantly more frequent among patients with PGF (88.6% versus 71.8% p = 0.025). Thirty-two percent of patients with PGF were treated with increasing doses of thrombopoietin-receptor agonists (TRA) and 7 patients were treated with a donor CD34 + selected boost. In total, 93.2% of patients reached adequate peripheral blood counts in a median time of 101 days (range 11-475) after diagnosis. PGF is a frequent complication after haplo-SCT with PT-Cy. CMV reactivation might be the most relevant factor associated to its development. Even when most patients recover peripheral counts with support therapy, there is a group of patients with persistent cytopenias who can effectively be treated with TRA and/or a boost of CD34 + selective cells.

Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.

BACKGROUND: A variable incidence of profound cytopenia has been described in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). This complication leads to severe infection in some cases, especially those who present additional risk factors including prior hematopoietic stem cell transplantation (HSCT). STUDY DESIGN AND METHODS: We report a case of breakthrough invasive fungal infection in a patient with prolonged neutropenia after CAR-T cell therapy administered for relapsed B-cell ALL after allogeneic haploidentical HSCT. RESULTS: After disease progression was discarded, therapy with antifungal agents, G-CSF and thrombopoietin analogue was started. However, no sign of haematological recovery or infection improvement was observed. A fresh mobilized selected CD34-stem cell boost from her haploidentical transplant donor was infused without further conditioning. Within 15 days of mobilized CD34-boost administration the patient showed complete resolution of both the aplasia and fungal infection. DISCUSSION: This case illustrates as proof-of-concept the efficacy and safety of selected CD34-stem cell boost from prior donor as salvage treatment of prolonged cytopenias after CAR-T cell therapy.

Extracorporeal membrane oxygenation (ECMO) in adults with acute respiratory distress syndrome (ARDS): A 6-year experience and case-control study.

PURPOSE: To evaluate the development of an extracorporeal membrane oxygenation (ECMO) program for the treatment of acute respiratory distress syndrome (ARDS) in adults. METHODS: a) Descriptive study of 15 cases treated since the program approval from 2010 to 2016. b) Case-control study matching the 15 ECMO cases with the 52 severe ARDS treated between 2005 and 2011 in which alternative rescue treatments (prone ventilation, tracheal gas insufflation (TGI) and/or the administration of inhaled nitric oxide (iNO)) were used. RESULTS: ECMO experience: Mortality 47% (7/15). Four patients died due to complications directly related to ECMO therapy. ICU stay 46.6 ± 45 days (range 4-138). Hospital stay 72.4 ± 98 days (range 4-320). Case-control: The mortality in the control group was 77% (44/52). The ECMO group practically doubled the mean days of ICU and hospital stay (p < 0.05). The multivariate analysis demonstrated an OR of 0.13 (0.02-0.73) for mortality associated with ECMO treatment. The following were also independent predictors of mortality: age (OR 1.05, 95% CI 1-11), SOFA score (OR 1.34, 95% CI 1.04-1.7), and the need for renal replacement therapy (OR 1.3, 95% CI 1.04-1.7). Economic analysis: The hospital cost per patient in the ECMO group doubled compared to that of the control group (USD 77,099 vs USD 37,660). However, the cost per survivor was reduced by 4% (USD 144,560 vs USD 150,640, respectively). CONCLUSIONS: Our results endorse the use of ECMO as a rescue therapy in adults with ARDS, although there are some risks associated with a learning curve as well as an important increase in the days of patient stay. The justification for the maintenance of an ECMO program in adults should be based on future studies of efficacy and cost effectiveness.