Impact of hHLA-DPB1 matching on clinical outcomes after haploidentical-related hematopoietic stem cell transplantation

ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

Validation of the Effectiveness and Safety of Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas: 10-year Experience of a Single Institution

This study was performed to validate the effectiveness and safety of concurrent chemoradiotherapy and adjuvant therapy with temozolomide for newly diagnosed glioblastoma multiforme as a standard treatment protocol. Between 2004 and 2011, patients newly diagnosed with glioblastoma who were treated with temozolomide during concurrent chemoradiotherapy and adjuvant chemotherapy were included from a single institution and analyzed retrospectively. The primary endpoint was overall survival, and the secondary endpoints were progression-free survival, response, and safety. A total of 71 patients were enrolled in this study. The response rate was 41% (29/71), and the tumor control rate was 80% (57/71). In the 67 patients who completed the concurrent chemoradiotherapy with temozolomide, the median overall survival was 19 months and the 1- and 2-yr overall survival rates were 78.3% and 41.7%, respectively. The median progression free survival was 9 months, and the 1- and 2-yr progression free survival rates were 33.8% and 14.3%, respectively. The mean duration of survival after progression of disease in salvage treatment group was 11.9 (1.3-53.2) months. Concurrent chemoradiotherapy with temozolomide resulted in grade 3 or 4 hematologic toxic effects in 2.8% of the patients. The current protocol of temozolomide during and after radiation therapy is both effective and safe and is still appropriate as the standard protocol for treatment of glioblastoma. An active salvage treatment might be required for a better prognosis.

Estratificación de riesgo de morbimortalidad en pacientes neutropénicos febriles hematooncológicos utilizando dos escalas de predicción / Risk stratification of mortality in patients febrile neutropenic hemato using two scales prediction

Determinar el pronóstico de mortalidad en los pacientes hematooncológicos con neutropenia febril a través del score de MASCC y el de PARK. Se realizó un estudio descriptivo, prospectivo constituido por 34 pacientes hematooncológicos, neutropénicos febriles hospitalizados del Hospital Universitario de Caracas, a quienes se aplicaron ambos score. No se halló correlación estadística. Sin embargo, se observó que en el grupo de bajo riesgo según el score de MASCC estuvieron todos los pacientes que fallecieron, mientras que según el score de PARK fallecieron principalmente los pacientes con valor de PCR mayor o igual a 20. El score de MASCC pareciera no ser una herramienta útil para evaluar pronóstico en estos pacientes, siendo probablemente más útil el score de PARK en especial el valor de PCR en el ingreso...

To determine the mortality prognosis in hematooncologic neutropenic febrile patients using MASCC and Park scores. Both scores were applied to 34 hospitalized patients of the Hospital Universitario de Caracas, Venezuela, in a descriptive, prospective study. No statistic correlation was found. However we found that that the patients who died were clasiffied as low risk by the Score of MASCC and had PCR values of 20 or more Parks score. MASCC ìs score seems not to be a useful tool to evaluate the prognosis of these patients versus the Park ìs, score wich was more useful especially taking in account the PCR value on the first day of admission...

Sobrevida de pacientes submetidos a transplante alogênico de medula óssea / Survival of patients submittes to allogeneic boné marrow transplantation

Introdução: O transplante de células-tronco hematopoiéticas (TCTH) alogênico é um procedimento que oferece um potencial de cura para doenças hematológicas malignas e benignas. O benefício da técnica está especialmente relacionado ao aumento da sobrevida em pacientes com doadores HLA-compatíveis em cujos casos o tratamento quimioterápico mostrou-se insuficiente ou ineficaz. Objetivos: Analisar a sobrevida de pacientes que receberam TCTH alogênico aparentado no Serviço de Hematologia Clínica e Transplante de Medula Óssea (SHCTMO) do Hospital de Clínicas de Porto Alegre (HCPA). Métodos: Estudo de coorte prospectiva com análise de sobrevida de pacientes transplantados entre 1994 e 2003. Resultados: Foram analisados 133 pacientes com idade média de 30,8±14,8 anos com um tempo médio de 26,8 meses entre o diagnóstico e o TCTH. Cinco anos após o transplante, 71 pacientes (53,4%) estavam vivos, 22 pacientes tinham leucemia mieloide aguda (LMA), 54, leucemia mieloide crônica (LMC), e seis padeciam de síndrome mielodisplásica (SMD), sendo que, em 5 anos, a sobrevida foi de 52, 50 e 33%, respectivamente. Dos 26 pacientes transplantados por anemia aplásica (AA), 66,7% tinham idade inferior a 20 anos, e 61,5% dos que tinham mais de 20 anos estavam vivos. Conclusão: Embora, no nosso estudo, o tempo médio entre o diagnóstico e o transplante tenha sido superior a 2 anos, e embora nossa análise tenha sido apenas estratificada pelo tipo da doença, independentemente do regime de condicionamento ou da fase da doença no momento do TCTH, nossos resultados são superponíveis aos descritos na literatura mundial.

Background: Hematopoietic stem cell transplantation (HSCT) represents a curative alternative for malignant and benign hematological diseases. The benefits of the technique are especially related to an increase in the survival of patients with HLA-compatible hematopoietic stem cell donors when chemotherapy or clinical therapy has resulted ineffective. Objectives: To analyze the survival of patients submitted to allogeneic HSCT at the Hematology and Bone Marrow Transplant Service of Hospital de Clínicas de Porto Alegre. Methods: A prospective cohort of all patients submitted to transplantation between 1994 and 2003 was analyzed for overall survival. Results: A total of 133 patients were submitted to transplantation in the study period, with a mean age of 30.8±14.8 years; mean time elapsed between diagnosis and transplant was 26.8 months. Five years after the procedure, 71 patients (53.4%) were alive, 22 patients had acute and 54 had chronic myeloid leukemia, and six patients presented myelodysplastic syndrome; the 5 year overall survival was 52, 50, and 33%, respectively. Of the 26 patients transplanted for aplastic anemia, 66.7% had 20 or less years of age, and 61.5% of the patients older than 20 years were alive. Conclusion: Although the mean time elapsed between diagnosis and transplantation was over 2 years and although our results were stratified by type of disease only, the findings herein reported are similar to those found in the literature, independently of conditioning regimen or disease stage at the time of transplant.

Hematological manifestations of congenital cytomegalovirus infection.

Nine infants suffering from congenital cytomegalovirus infection were studied for clinical features with special reference to hematological manifestations. The mean age of appearance of first clinical symptom of disease was 14 days and mean age at presentation was 58 days. Significant pallor, thrombocytopenia and evidence of hemolysis were present in 8 (89%), 4 (44%) and 4 (44%) patients respectively out of three bone marrow examination performed, paucity of erythroid and megakaryocytic cells were seen in two. The other clinical features included hepatomegaly in a (100%) splenomegaly in 6 (66%) each, petachial rash in 5 (55%), Hepatitis in 4 (44%) optic atrophy and corneal opacities in one patient each. Two patients died. Remaining patients showed symptomatic improvement without specific therapy.