Peripheral blood stem cell versus bone marrow graft for patients ≥60 years undergoing reduced intensity conditioning haploidentical transplantation for acute myeloid leukemia in complete remission: An analysis of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

In the context of T-cell replete haploidentical stem cell transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy), it is still unknown whether peripheral blood (PB) or bone marrow (BM) is the best graft source. While PB is associated with a higher incidence of graft-versus-host disease (GVHD), it may induce a stronger graft-versus-leukemia effect compared to BM, notably in acute myeloid leukemia (AML). From the EBMT registry database, we compared T-cell replete PB (n = 595) versus BM (n = 209) grafts in a large cohort of 804 patients over the age of 60 years who underwent Haplo-SCT with PT-Cy for an AML in first or second complete remission. The risk of acute GVHD was significantly higher in the PB group (Grade II-IV: HR = 1.67, 95% CI [1.10-2.54], p = 0.01; Grade III-IV: HR = 2.29, 95% CI [1.16-4.54], p = 0.02). No significant difference was observed in chronic GVHD or non-relapse mortality. In the PB group, the risk of relapse was significantly lower in the PB group (HR = 0.65, 95% CI [0.45-0.94], p = 0.02) and leukemia-free survival was significantly better (HR = 0.76, 95% CI [0.59-0.99], p = 0.04), with a trend toward better overall survival (HR = 0.78, 95% CI [0.60-1.01], p = 0.06). We conclude that in the specific context of Haplo-SCT with PT-Cy, PB grafts represent a valid option to decrease the risk of relapse and improve outcome of older AML patients who usually do not benefit from conditioning intensification.

Feasibility of allogeneic hematopoietic stem cell transplantation in advanced age.

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.

Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT.

We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML.

Critical patients COVID-19 has changed the management and outcomes in the ICU after 1 year of the pandemic? A multicenter, prospective, observational study.

OBJECTIVE: To compare the clinical characteristics, treatments, and evolution of critical patients with COVID-19 pneumonia treated in Intensive Care Units (ICU) after one year of pandemic. METHODOLOGY: Multicenter, prospective study, which included critical COVID-19 patients in 9 ICUs in northwestern Spain. The clinical characteristics, treatments, and evolution of patients admitted to the ICU during the months of March-April 2020 (period 1) were compared with patients admitted in January-February 2021 (period 2). RESULTS: 337 patients were included (98 in period 1 and 239 in period 2). In period 2, fewer patients required invasive mechanical ventilation (IMV) (65% vs 84%, p < 0.001), using high-flow nasal cannulas (CNAF) more frequently (70% vs 7%, p < 0.001), ventilation non-invasive mechanical (NIMV) (40% vs 14%, p < 0.001), corticosteroids (100% vs 96%, p = 0.007) and prone position in both awake (42% vs 28%, p = 0.012), and intubated patients (67% vs 54%, p = 0.034). The days of IMV, ICU stay and hospital stay were lower in period 2. Mortality was similar in the two periods studied (16% vs 17%). CONCLUSIONS: After 1 year of pandemic, we observed that in patients admitted to the ICU, CNAF, NIMV, use of the prone position, and corticosteroids have been used more frequently, reducing the number of patients in IMV, and the length of stay in the ICU and hospital stay. Mortality was similar in the two study periods.

[Critical patients COVID-19 has changed the management and outcomes in the ICU after 1 year of the pandemic? A multicenter, prospective, observational study]. / Pacientes críticos COVID-19. ¿Han variado el manejo y los resultados en la UCI tras un año de pandemia? Estudio multicéntrico, prospectivo, observacional.

Objective: To compare the clinical characteristics, treatments, and evolution of critical patients with COVID-19 pneumonia treated in intensive care units (ICU) after one year of pandemic. Methodology: Multicenter, prospective study, which included critical COVID-19 patients in 9 ICUs in northwestern Spain. The clinical characteristics, treatments, and evolution of patients admitted to the ICU during the months of March-April 2020 (period 1) were compared with patients admitted in January-February 2021 (period 2). Results: 337 patients were included (98 in period 1 and 239 in period 2). In period 2, fewer patients required invasive mechanical ventilation (IMV) (65% vs. 84%, P < .001), using high-flow nasal cannulas (CNAF) more frequently (70% vs. 7%, P < .001), ventilation non-invasive mechanical (NIMV) (40% vs. 14%, P < .001), corticosteroids (100% vs. 96%, P = .007) and prone position in both awake (42% vs. 28%, P = .012), and intubated patients (67% vs. 54%, P = .034). The days of IMV, ICU stay and hospital stay were lower in period 2. Mortality was similar in the two periods studied (16% vs. 17%). Conclusions: After one year of pandemic, we observed that in patients admitted to the ICU, CNAF, NIMV, use of the prone position, and corticosteroids have been used more frequently, reducing the number of patients in IMV, and the length of stay in the ICU and hospital stay. Mortality was similar in the two study periods.

CNS Involvement at Initial Diagnosis and Risk of Relapse After Allogeneic HCT for Acute Lymphoblastic Leukemia in First Complete Remission.

Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CNS-negative, have not been compared. Here, we evaluated outcomes of 547 patients (CNS-positive = 96, CNS-negative = 451) who were allografted in the first complete remission (CR1) between 2009 and 2019. Primary endpoint was leukemia-free survival (LFS). Median follow-up was not different between the CNS-positive and CNS-negative groups (79 versus 67.2 months, P = 0.58). The CNS-positive group were younger (median age 31.3 versus 39.7 years, P = 0.004) and were allografted more recently (median year 2012 versus 2010, P = 0.003). In both groups, MAC was the preferred approach (82.3% versus 85.6%, P = 0.41). On multivariate analysis, the CNS-positive group had higher incidence of relapse (RI) (hazard ratio [HR] = 1.58 [95% confidence interval (CI) = 1.06-2.35], P = 0.025), but no adverse effect on LFS (HR = 1.38 [95% CI = 0.99-1.92], P = 0.057) or overall survival (OS) (HR = 1.28 [95% CI = 0.89-1.85], P = 0.18). A subgroup multivariate analysis limited to CNS-positive patients showed that a TBI-based MAC regimen resulted in better LFS (HR = 0.43 [95% CI = 0.22-0.83], P = 0.01) and OS (HR = 0.44 [95% CI = 0.21-0.92], P = 0.03) and lower RI (HR = 0.35 [95% CI = 0.15-0.79], P = 0.01). Another subgroup analysis in CNS-negative patients showed that MAC-TBI preparative regimens also showed a lower RI without a benefit in LFS or OS. While a MAC-TBI allo-HCT regimen may not be suitable to all, particularly for older patients with comorbidities, this approach should be considered for patients who are deemed fit and able to tolerate.

Hipotiroidismo asociado al uso de talidomida / Thalidomide-induced hypothyroidism

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Experimental models for cardiac regeneration.

Simple ex vivo or in vitro models are most useful for testing putative cell therapy protocols, as they allow quick and controlled screening of variants and possible improvements. We discuss here three different models: coculture of precursors of human bone marrow cells (BMCs) with mouse heart slices bearing a cryogenic lesion; coculture of human BMCs and rat cardiomyocytes separated by a porous membrane that allows passage of soluble substances but prevents migration of nuclear material; and injection of human BMCs in developing chick heart bearing burn lesions. Our results indicate that the damaged areas express specific genes such as MPC1 and SDF1, and that some human BMCs migrate and graft near the lesion, where they can originate cells with a cardiac phenotype that produce human cardiac proteins. The frequency of this transformation is, however, very low. Understanding the factors that determine and regulate nuclear reprogramming and transdifferentiation would be crucial to appraising the contribution of these phenomena to cardiac regeneration and, eventually, to modulating them with therapeutic intent.