Extramedullary T-lymphoblastic Crisis in a Myelodysplastic/Myeloproliferative Neoplasm with a t(12;22)/MN1::ETV6 Translocation.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are not a single disease, but rather a heterogenous group of entities which are increasingly subclassified according to recurrent genetic abnormalities. Chromosomal translocations involving meningioma 1 (MN1) and ETS variant 6 (ETV6) genes are extremely rare, but recurrent in myeloid neoplasms. We describe the case of a patient with a myelodysplastic/myeloproliferative neoplasm with neutrophilia, who developed an extramedullary T-lymphoblastic crisis with the t(12;22)(p13;q12) translocation as the only cytogenetic abnormality. This case shares several clinical and molecular features with myeloid/lymphoid neoplasms with eosinophilia. The treatment of this patient was challenging, as the disease proved to be highly refractory to chemotherapy, with allogenic stem cell transplantation as the only curative option. This clinical presentation has not been reported in association with these genetic alterations and supports the concept of a hematopoietic neoplasm originating in an early uncommitted precursor cell. Additionally, it stresses the importance of molecular characterization in the classification and prognostic stratification of these entities.

How Allogeneic Hematopoietic Stem Cell Transplantation has Evolved Over Time: 30-Years' Experience at a Single Institution.

INTRODUCTION: Allogeneic stem cell transplantation is an established procedure for a variety of diseases of the hematopoietic system. Our transplant program started in 1987 and since then advances have been made in the care of patients undergoing transplantation. We conducted a study to evaluate whether the changes implemented over time have improved the outcomes of transplantation. MATERIAL AND METHODS: We analyzed changes in patients, cell source, transplantation and outcome among 682 consecutive patients receiving their first transplant between 1987 and 2016. We compared overall survival, progression-free survival, the incidence of nonrelapse mortality and relapse in 10-year cohorts over the three decades of the study. RESULTS: The median age of transplanted patients, the use of peripheral blood and unrelated donors all increased very significantly. There was an increase in the number of high-risk patients when comparing the first decade with the two subsequent ones. The 3-year non-relapse mortality decreased significantly from 29% to 20% (p = 0.045), while the overall survival, progression free survival and cumulative incidence of relapse remained stable. DISCUSSION: Allogeneic hematopoietic stem cell transplantation has evolved considerably since its introduction in clinical practice. In the present study, we evaluated how these changes affected our practice along 30 years of activity and compared the results with those published in the literature. CONCLUSION: Despite increasing age, higher risk patients and the increasing use of unrelated donors our results show a continuous significantly reduced non-relapse mortality, with stable overall survival, progression free survival and relapse rate.

Introdução: A transplantação alogénica de células hematopoiéticas é utilizada regularmente no tratamento de uma grande variedade de doenças hematológicas. O nosso programa de transplantação teve início em 1987 e desde então têm sido numerosos os avanços nesta área. Este estudo foi conduzido para avaliar se as alterações introduzidas ao longo de 30 anos melhoraram os resultados obtidos. Material e Métodos: Analisámos os resultados numa população de 682 doentes submetidos consecutivamente a um primeiro transplante alogénico entre 1987 e 2016. Para tal, os doentes foram divididos em intervalos de 10 anos e comparámos a sobrevida global, a sobrevida livre de progressão, a mortalidade não associada a recaída e as recaídas em cada década do estudo. Resultados: A mediana de idades dos doentes transplantados, a utilização de células progenitoras provenientes do sangue periférico e a transplantação com dadores não familiares aumentaram muito significativamente ao longo do estudo. Verificou-se, comparativamente com a primeira década, um aumento do número de doentes de alto risco nas duas décadas subsequentes. A mortalidade não relacionada com recidiva, avaliada aos três anos pós-transplante, diminuiu significativamente de 29% para 20% (p = 0,045), mantendo-se estáveis a sobrevida global e a sobrevida livre de progressão, assim como a incidência cumulativa de recaídas. Discussão: A transplantação alogénica hematopoiética tem evoluído consideravelmente desde a sua introdução na prática clínica. No presente trabalho são avaliados os reflexos dessa evolução ao longo de 30 anos sendo analisados os resultados obtidos e comparados com os referidos na literatura. Conclusão: Apesar das características mais desfavoráveis verificadas ao longo das três décadas (doentes mais idosos, doenças de risco mais elevado, aumento do número de dadores não familiares) foi possível reduzir significativamente a mortalidade associada ao procedimento, mantendo-se estáveis a sobrevida global e livre de progressão, assim como a incidência de recaídas.

Is cancer latency an outdated concept? Lessons from chronic myeloid leukemia.

Our concept of cancer latency, the interval from when a cancer starts until it is diagnosed, has changed dramatically. A prior widely-used definition was the interval between an exposure to a cancer-causing substance and cancer diagnosis. However, this definition does not accurately reflect current knowledge of how most cancers develop assuming, mostly incorrectly, one exposure is the sole cause of a cancer, ignoring the possibility the cancer being considered would have developed anyway but that the exposure accelerated cancer development and eliding the randomness in when a cancer is diagnosed. We show, using chronic myeloid leukaemia as a model, that defining cancer latency is not as simple as it once seemed. It is difficult or impossible to know at which event or mutation to start to clock to measure cancer latency. It is equally difficult to know when to stop the clock given the stochastic nature of when cancers are diagnosed. Importantly, even in genetically-identical twins with the same driver mutation intervals to develop cancer vary substantially. And we discuss other confonders. Clearly we need a new definition of cancer latency or we need to abandon the concept of cancer latency in the modern era of cancer biology.

Widespread skin nodules as a manifestation of breakthrough invasive aspergillosis in a bone marrow transplant patient.

Invasive aspergillosis (IA) is a life-threatening complication of bone marrow transplantation manifesting most often as a respiratory tract infection with potential hematogenous dissemination to any organ. The authors report an unusual case of IA manifesting as widespread subcutaneous nodules, with intact overlying skin, complicating pulmonary infection in a transplanted patient who received mold-active antifungal prophylaxis. The present case emphasizes the relevance of cellular immunity, in particular T lymphocytes, in the control of invasive fungal disease and highlights the potential role of positron emission tomography scan in assessing its dissemination.

Alternaria alternata invasive fungal infection in a patient with Fanconi's anemia after an unrelated bone marrow transplant.

Alternaria spp. have emerged as opportunistic pathogens particularly in immunosuppressed patients, such as bone marrow transplant recipients. The authors present a case of Alternaria alternata in a patient with Fanconi's anemia, who received antifungal prophylaxis with posaconazole after an unrelated bone marrow transplantation, followed by empirical antifungal treatment with caspofungin when persistent fever emerged until cutaneous lesions eventually appeared. At that time there were clinical reasons to assume that the patient had an infection with an emerging fungus. This consideration triggered a change of the antifungal therapy from caspofungin to liposomal amphotericin B. After collecting sufficient evidence for the presence of an invasive fungal infection by A. alternata and given the severity of neutropenia and other immunosuppression, oral posaconazole was added to liposomal amphotericin B. The course of disease in this case suggests a possibly synergistic interaction between liposomal amphotericin B and posaconazole when administered simultaneously to treat an invasive systemic infection by Alternaria spp. in immunocompromised patients.

[High dose chemotherapy with autologous stem-cell support in germ cell tumors: The Instituto Português de Oncologia de Lisboa Francisco Gentil Series]. / Quimioterapia de alta dose com suporte hematopoiético autólogo em tumores de células germinativas Experiência do Instituto Português de Oncologia de Lisboa Francisco Gentil.

BACKGROUND: High dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) has been administered to patients with high-risk germ cell tumours (GCT). The role of this treatment for GCT still remains unclear, including the identification of subgroups more likely to benefit from such strategy. METHODS: A retrospective review was conducted of all male patients with gonadal and extra gonadal GCT treated with HDCT-ASCT between 1996 and 2008 at the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG). RESULTS: Twenty patients were treated with HDCT-ASCT, 17 with primary testicular tumours, two mediastinal and one retroperitoneal GCT. According to the International Germ Cell Cancer Consensus Group (IGCCCG) classification, at diagnosis three patients had good risk, four intermediate, eight poor but for the patients left the risk group could not be ascertained. In eight patients HDCT-ASCT was used upfront, after induction with first-line conventional chemotherapy, and in the remaining 12 for relapsed GCT. One patient had platinum-resistant and another platinum-refractory disease. Only two patients had Beyer score > 2. All but one patient were treated with ICE (Ifosfamide, Carboplatin, Etoposide). Six patients underwent a second HDCT-ASCT course. The 5-year overall survival and progression free survival were respectively 53% and 44%; both patients with mediastinal GCT are long term survivors. CONCLUSION: Randomized studies to date have failed to indicate a survival advantage for HDCT-ASCT in GCT. This series is small and heterogeneous which prevents us from drawing conclusions regarding the benefit of this treatment for GCT. However, we could confirm the lack of benefit of HDCT-ASCT for platinum-resistant GCT and to question the absolute contraindication to this therapeutic modality in mediastinal GCT. HDCT-ASCT should therefore be performed exclusively in experienced centers and, preferably, in the setting of clinical trials.