Sequence matters: Total body irradiation (TBI)-based myeloablative conditioning with post-transplant cyclophosphamide may reduce the early nonrelapse mortality compared with pretransplant cyclophosphamide plus TBI.

OBJECTIVES: High-dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo-SCT). We retrospectively compared the main outcomes of an HLA matched or 1-allele mismatched related or unrelated allo-SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). METHODS: Fifty-nine patients received cyclophosphamide (Cy)-TBI (13.5 Gy) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin-inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine-TBI (8.8-13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI-PTCy group). RESULTS: Median follow-up for survivors was 82 and 22 months. The 12-month probability of overall survival and progression-free survival were similar (p = .18, p = .7). The incidence of Grades 2-4 and 3-4 acute GVHD, and the incidence of moderate-to-severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD-free and relapse-free patients without systemic immunosuppression (GRFS) at 1-year posttransplant was higher in the FluTBI-PTCy group (p = 0.01). CONCLUSIONS: The study confirms the safety and efficacy of a novel FluTBI-PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.

Successful Outcome in Patients with Myelofibrosis Undergoing Allogeneic Donor Hematopoietic Cell Transplantation Using Reduced Doses of Post-Transplantation Cyclophosphamide: Challenges and Review of the Literature.

Engraftment and nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT) depend greatly on the transplantation platform in patients with myelofibrosis (MF). We report outcomes of 14 consecutive MF patients who received reduced doses of post-transplantation cyclophosphamide (PTCy; 60 mg/kg total dose) and tacrolimus as graft-versus-host disease (GVHD) prophylaxis as part of a new standardized allo-HCT protocol. The median patient age at allo-HCT was 59 years (range, 41 to 67 years), and the median interval from diagnosis to HCT was 19 months (range, 2 to 114 months). All patients received ruxolitinib before HCT, and 71% had no response. Most patients (78%) had symptomatic splenomegaly at HCT. Eighty-six percent received reduced-intensity conditioning, and 64% underwent allo-HCT from an unrelated donor. There were no graft failures, and neutrophil and platelet recovery occurred at a median of 21 days and 31 days, respectively. The cumulative incidence of grade II-IV acute GVHD was 28.6%, and that of grade III-IV acute GVHD was 7%. The 2-year incidence of overall and moderate-severe chronic GVHD was 36% and 14%, respectively. Only 1 patient relapsed after transplantation, and NRM was 7% at 100 days and 14% at 2 years. The GVHD-free/relapse-free and immunosuppression-free incidence at 1 year was 41%. With a median follow-up for survivors of 28 months (range, 8 to 55 months), the 2-year overall survival and progression-free survival were 86% and 69%, respectively. Reduced doses of PTCy as GVHD prophylaxis for high-risk MF patients showed promising results by reducing the incidence of GVHD without any cases of graft failure.

Early heart rate variations during head-up tilt table testing as a predictor of outcome of the test.

Head-up tilt table testing (HUTT) is a useful tool for the diagnosis of unknown origin of syncope. A setback is its duration. This study tries to establish a specific parameter that, according to the heart rate elevation in the test's initial phase, allows a reliable prediction of its outcome. In a prospective study, every patient being under unknown syncope workup was included. A two-phase 20-minute tilt table test was performed. The initial phase was passive, and the second required pharmacological stimulation with isoproterenol. The basal and 5- and 10-minute heart rate values of the passive phase were measured and compared within the group and against negative tests. During a 1-year period, 115 HUTT were performed: 88 were positive and 27 negative. The negative HUTT patients had an increase in HR of 5.05 (+/- 13.5) beats/min at 5 minutes, and 5.79 (+/- 12.9) beats/min at 10 minutes (P = 0.2). Those with a positive HUTT had an increase of 9.05 (+/- 14.5) beats/min at 5 minutes, and of 10 (+/- 13.4) beats/min at 10 minutes (P < 0.001). There were no significant changes in HR when comparing positive to negative HUTT. There is no specific number that allows predication of outcome early in HUTT. Within the group, variations are important. Only a group tendency can be established, which strongly correlates with the results obtained during the test.

[Use of 2-dimensional echocardiography in the diagnosis of interventricular septum rupture following myocardial infarction]. / Valor del ecocardiograma bidimensional en el diagnóstico de la ruptura del septum interventricular post-infarto del miocardio.

Interventricular septal rupture is a rare complication of the acute myocardial infarction. We report a case with rupture 4 weeks after diaphragmatic wall necrosis. The patient developed heart failure, precordial murmur and clinical signs of left-to-right shunt. The septal rupture was detected by two-dimensional echocardiogram and confirmed by catheterization. The surgical correction of the defect, was successful.

[Diagnostic problems in visceral heterotaxia]. / Problemas diagnósticos en heterotaxia visceral

Due to the lack of uniformity in the criteria for formulating the diagnosis of the syndrome of heterotaxy, 12 cases with this abnormality were reviewed. The patients were selected on the following basis: symmetrical liver, changeable P waves in consecutive electrocardiograms, bronchial isomerism, hematological disturbances, anomalous relationship of the inferior vena cava and abdominal aorta, anomalous systemic and pulmonary venous drainage and complex cardiac malformations. The most frequent findings were: symmetrical liver, changeable P waves, anomalous systemic venous return, anomalies of the atrio-ventricular valves, particularly atrioventricular canal, aorto-cava juxtaposition, single atrium, anomalous pulmonary venous return, transposition of the great arteries and pulmonary stenosis. Less frequent anomalies were: atrial and ventricular septal defects, atrial isomerism, truncus arteriosus and partial distortion of the great arteries. The hematological disturbances as well as the radioisotope scanning of the liver and the spleen were of little help. Suggestions are given for the diagnosis of the syndrome and for the evaluation of present diagnostic procedures making necessary to use the data gathered with more precision.