[ABO incompatibility and complications in hematopoietic stem cell transplantation]. / Incompatibilidad ABO en el trasplante de células progenitoras hematopoyéticas y sus complicaciones.

Background: Hematopoietic stem cell transplants (HSCT) can be performed regardless of the ABO group compatibility between donor and recipient. ABO incompatibility in HSCT is related to pure red cell aplasia (PRCA), or passenger lymphocyte syndrome. The impact of ABO incompatibility on graft-versus-host disease and transplant-related mortality is controversial due to the heterogeneity of procedures carried out in different transplant centers. Objective: To determine the prevalence of ABO incompatibility and its complications in a hematopoietic stem transplant unit. Material and methods: An observational, retrospective study was carried out in patients undergoing HSCT from January 2014 to January 2020. All trasplant patients were included. Qualitative variables were analyzed using chi-squared test, and Wilcoxon and Student's t tests were used for quantitative variables. A p < 0.05 was considered significant. Results: 124 patients undergoing HSCT were analyzed, out of which 31 had ABO incompatibility, with a punctual prevalence of 24.4%; among them, 54% presented with major incompatibility, 32% minor incompatibility and 13% bidirectional incompatibility. Three cases of PRCA were reported. There were no differences in survival at one year in both groups. Conclusions: The ABO incompatibility ant its complications were not related to the increase in mortality. Randomized prospective studies are required to define the role of ABO incompatibility in HSCT prognosis.

Introducción: los trasplantes de células progenitoras hematopoyéticas (TCPH) se pueden hacer independientemente de la compatibilidad de grupo sanguíneo ABO entre donador y receptor. La incompatibilidad ABO (IABO) en los TCPH puede presentar complicaciones, como aplasia pura de serie roja (APSR), o síndrome de linfocito pasajero. El impacto de la IABO en la enfermedad del injerto en contra del huésped y la mortalidad relacionada al trasplante es controversial por la heterogeneidad de procedimientos que se hacen en los distintos centros de trasplante. Objetivo: determinar la prevalencia de la IABO y sus complicaciones en los pacientes trasplantados en una unidad de trasplante de progenitores hematopoyéticos. Material y métodos: se hizo un estudio tipo observacional, descriptivo, en pacientes sometidos a TCPH de enero de 2014 a enero de 2020. Se incluyeron todos los pacientes trasplantados. Las variables cualitativas se analizaron con chi cuadrada y para las variables cuantitativas se usó la prueba de Wilcoxon y t de Student. Una p < 0.05 fue significativa. Resultados: se analizaron 124 pacientes sometidos a TCPH y 31 de ellos presentaron IABO, con una prevalencia puntual de 24.4%; entre ellos, 54% presentaron incompatibilidad mayor, 32% incompatibilidad menor y 13% incompatibilidad bidireccional. Se reportaron tres casos de APSR. No hubo diferencias en la supervivencia global a un año en ambos grupos. Conclusiones: la IABO y sus complicaciones no se relacionaron con aumento en la mortalidad. Se requieren estudios prospectivos aleatorizados para definir el papel de la IABO con el pronóstico del trasplante.

Relapsing Myopathy With Granulomatous Inflammation as Chronic Graft vs Host Disease Feature: A Case Report.

BACKGROUND: Graft-vs-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant. Myopathy is a rare neuromuscular sign of chronic GVHD, with an incidence of less than 4% in all patients. The data are heterogeneous, and no standard criteria exists for diagnosis or treatment. CASE REPORT: We present the case of an 18-year-old man with acute lymphoblastic leukemia, who developed myopathy associated with GVHD 19 months after allogeneic hematopoietic stem cell transplant from an unrelated donor. The patient had a previous history of acute cutaneous and chronic hepatic GVHD. At the time of symptom onset, the immunosuppressive drugs were tapered. He developed with sudden symmetrical proximal muscle weakness that prevented him from walking. Diagnosis was confirmed using magnetic resonance imaging, electromyography, muscle enzymes, and muscle biopsy results. He initially responded to immunosuppressive therapy but relapsed after quick tapering of prednisone, requiring a prolonged course of steroids and an additional dose of immune globulin intravenous. At the moment of the publication, the patient has 9 months free from GVHD relapse. CONCLUSIONS: GVHD-associated myopathy is a rare complication of hematopoietic stem cell transplant and must be suspected in patients with sudden proximal muscle weakness and moderate pain. Diagnosis is challenging and must include magnetic resonance imaging, electromyography, muscle enzymes, and muscle biopsy results. Usually, all patients respond adequately to immunosuppression.

Isolated Renal Relapse in a Post-Allogenic Transplant Adult Patient With Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is an aggressive hematological neoplasm typically more common in children than adults. More prolonged remissions and a potential cure can be achieved if allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Outcomes after allo-HSCT vary significantly among patients, and multiple factors contribute to these outcomes. Isolated extramedullary relapse (iEMR) after allo-HSCT is rare. We present the case of a 43-year-old man who was diagnosed with Philadelphia chromosome-negative (Ph-neg), B-cell ALL and underwent haploidentical allo-HSCT because of high-risk features at diagnosis. One year later, he was admitted to the hospital with facial and peripheral edema, proteinuria, elevated serum creatinine levels, and hypertension. Renal biopsy was performed immediately. Renal infiltration of TdT+ leukemic cells was detected by immunohistochemistry. Bone marrow aspiration, lumbar puncture, and computed tomography (CT) scans were performed to identify other sites of possible relapse. No other sites were identified, and an extramedullary isolated renal relapse was diagnosed. Intensive re-induction with chemotherapy was not possible because of the coronavirus disease 2019 (COVID-19) infection. Six weeks later, a medullary relapse was noted. Medullary infiltration of B-cell ALL after allo-HSCT has a historically poor prognosis; however, iEMR appears to have a better overall prognosis. The optimal treatment for renal iEMR is still a matter of debate.

Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.

PROBLEM: We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. METHOD OF STUDY: Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes. RESULTS: Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months. CONCLUSION: We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.

Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy.

BACKGROUND: Among women with hypertensive disorders of pregnancy, biomarkers may stratify risk for developing preeclampsia with severe features (sPE). METHODS: Across 18 U.S. centers, we prospectively measured the ratio of serum soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in pregnant women hospitalized between 23 and 35 weeks of gestation. The primary outcome was predicting sPE, and secondary outcomes included predicting adverse outcomes within 2 weeks. The prognostic performance of the sFlt-1:PlGF ratio was assessed by using a derivation/validation design. RESULTS: A total of 1014 pregnant women were evaluated; 299 were included in the derivation cohort and 715 in the validation cohort. In the derivation cohort, the median sFlt-1:PlGF ratio was 200 (interquartile range, 53 to 458) among women who developed sPE compared with 6 (interquartile range, 3 to 26) in those who did not (P<0.001). The discriminatory ratio of ≥40 was then tested in the validation cohort and yielded a 65% positive (95% confidence interval [CI], 59 to 71) and a 96% negative (95% CI, 93 to 98) predictive value for the primary outcome. The ratio performed better than standard clinical measures (area under the receiver-operating characteristic curve, 0.92 versus <0.75 for standard-of-care tests). Compared with women with a ratio <40, women with a ratio ≥40 were at higher risk for adverse maternal outcomes (16.1% versus 2.8%; relative risk, 5.8; 95% CI, 2.8 to 12.2). CONCLUSIONS: In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of serum sFlt-1:PlGF provided stratification of the risk of progressing to sPE within the coming fortnight. (Funded by Cedars-Sinai Medical Center and Thermo Fisher Scientific; ClinicalTrials.gov NCT03815110.)