ABSTRACT
Introduction: Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin's lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor. Patients and Methods: We report on six patients with r/r HL, three patients with long-term follow-up, three newly treated, after biomodulatory therapy. All patients received MEPED (treosulfan 250 mg p.o. daily, everolimus 15 mg p.o. daily to achieve serum trough levels of 15 ng/ml, pioglitazone 45 mg p.o. daily, etoricoxib 60 mg p.o. daily and dexamethasone 0.5 mg p.o. daily). Patients had either received every at that time approved systemic treatment or were ineligible for standard treatment, including immune checkpoint inhibition (ICPi) due to prior demyelinating autoimmune polyneuropathy, myasthenia gravis and previous allogeneic hematopoietic-stem-cell transplant (alloHSCT). Medication was administered continuously from day 1. One patient with relapse after alloHSCT received trofosfamide 50 mg daily instead of treosulfan to avoid risk of increased myelotoxicity. The patients were treated in individual healing attempts outside a clinical trial after institutional review board approval. 18F-fluoro-2-deoxy-d-glucose positron emission tomography combined with computed tomography scan (FDG-PET/CT) was performed to monitor treatment and follow-up. Results: In the three newly treated patients, CT scans showed partial remissions after 2-5 months on MEPED treatment. Two patients had achieved PET Deauville score 2 and 3, while the third remained positive at Deauville score 5. One patient achieving PR became eligible for alloHSCT, while the other two patients continued treatment with MEPED. All patients eventually achieved continuous complete remission (cCR), one after consecutive alloHSCT, one after discontinuing MEPED consolidation for >1 year and one on on-going MEPED consolidation, respectively. Only one patient experienced Grade 3 toxicity (bacterial pneumonia) requiring temporary discontinuation of MEPED for 10 days. All three previously published patients received allo HSCT for consolidation and have achieved cCR. Conclusions: MEPED is well tolerated with low toxicity and highly efficacious in relapsed/refractory cHL, including severely comorbid patients. Due to its immunomodulatory components, MEPED might also have a synergistic potential when combined with ICPi but requires further evaluation within a clinical trial.
ABSTRACT
Demonstrar as características demográficas clínicas e taxas de sobrevida geral (SG) de pacientes tratados com transplante de células-tronco hematopoéticas (TCTH) autólogo no Vale do Paraíba-SP. Métodos - Análise retrospectiva de 129 pacientes atendidos no Hospital Pio XII de São José dos Campos entre 2005 e 2011. Coletaram-se registros de prontuário clínico, viabilidade das células CD34+ descongeladas,número de células CD34+ reinfundidas, reações adversas ao dimetilsulfóxido (DMSO), tempo de recuperação de contagem de neutrófilos (>0.5x109/L) e plaquetas (>20x109/L) e antimicrobianos prescritos. A SG 5 anos após o TCTH autólogo foi estimada para pacientes com mieloma múltiplo (MM), linfoma Hodgkin (LH) e linfoma não Hodgkin (LNH). Resultados - Foram selecionados 129 pacientes (67 homense 62 mulheres). A mediana das idades foi de 51 anos (18-70), 63 pacientes apresentavam MM, 25 LH, 24 LNH, 9 tumor germinativo, 7 leucemia mielóide aguda e 1 leucemia linfoblástica aguda. A mediana do número de células CD34+ reinfundidas foi de 6,02x106/kg (2,23-15,7) com viabilidade celular após descongelamento de 79% (62-93). O tempo para recuperação foi de 12 dias (9-18) para neutrófilose 13 dias (10-21) para plaquetas. Três pacientes apresentaram reações adversas ao DMSO. Trinta e três pacientes (25,6%) receberam antifúngico em associação aos antibióticos de amplo espectro de ação. As taxas de SG foram 57,7% (IC 33,8-71,5), 76,8% (IC 52,5-89,7) e 69,2% (IC 46,9-83,6) para MM, LH e LNH respectivamente. Conclusões - As características apresentadas demonstram que o TCTH autólogo é factível nesta região e as taxas de SG observadas em pacientes com MM, LH e LNH comparam-se favoravelmente com a literatura disponível...
To demonstrate the demographic and clinical aspects as well as the overall survival (OS) rates of patients treated with autologous stem cell transplantation (ASCT) in Vale do Paraíba-SP. Methods - Retrospective analysis of 129 patients from Pio XII Hospital of São José dos Campos that received treatment between 2005 and 2011. Data from the pronctuaries of the patients, number of CD34+ cells reinfused, viability of defrosted CD34+ cells, reactions induced by dimethylsulfoxide (DMSO), time to recover neutrophils and platelets count and antimicrobial agents prescribed were collected. Five-year OS was measured in patients with multiple myeloma (MM), Hodgkin´s lymphoma(HL) and non-Hodgkin´s lymphoma (NHL). Results - The median age was 51 years (18-70) among the 129 patients selected (67 male and 62 female). 63 had MM, 25 HL, 24 NHL, 9 germ cell tumors, 7 acute myeloid leukemia and 1 acute lymphoblastic leukemia. The median of number of CD34+ cells reinfused was 6.02 x 106/kg (2.23-15.7) with 79% (62-93%) of viable cells after defrost. Times to neutrophils and platelets count recovery were 12 (9-18) and 13 (10-21) days, respectively. Three patients showed DMSO-induced reactions. Thirty three patients(25.6%) were treated with antifungal in association with extended spectrum antibiotic. Five-year OS were 57.7% (CI 33.8-71.5) for MM patients, 76.8% (CI 52.5-89.7) for HL and 69.2% (CI 46.9-83.6) for NHL. Conclusions - The collected data provided evidence that the ASCT in Vale do Paraiba has favorable OS rates for patients with MM, HL and NHL in comparison to previously reported data from similar treatment in other regions...
