Catamenial pneumothorax: a rare manifestation of endometriosis.

Endometriosis is a common gynecological disease that primarily affects premenopausal women. It is mainly found in the pelvis but may be found at several extrapelvic locations. Thoracic endometriosis is a rare extrapelvic location of endometriosis and the leading cause of catamenial pneumothorax. We describe the case of a 35-year-old woman with a background of pelvic pain presenting to the emergency department with chest pain and dyspnea. The chest X-ray in the emergency department showed a large right-sided pneumothorax. Further imaging studies during patient evaluation revealed extensive fibrotic changes in the pelvis and well-defined solid nodules with high signal on T2 and T1-weighted images on MRI in abdominal and thoracic locations, rendering the diagnosis of a catamenial pneumothorax in a patient with pelvic, abdominal and thoracic endometriosis.

Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1ß protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1ß protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.

Haplo-identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: Results from the Severe Aplastic Anemia Working Party of the EBMT.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n = 123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n = 33) or T cells depleted in vivo with some type of graft manipulation ex vivo (n = 59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p = .22). Event-free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p = .046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p = .005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts.

[Preparing For the COVID-19 Pandemic: The Perspective of a Department of Anesthesiology in a Tertiary Hospital in Portugal]. / Preparação para a Pandemia COVID-19: A Perspetiva de um Serviço de Anestesiologia de um Hospital Terciário em Portugal.

Since the detection of the first cases of COVID-19, reported by the People's Republic of China on the 31st December 2019, up to the confirmation of the first cases in Portugal, on the 2nd March, countries like Italy and Spain faced the collapse of their healthcare systems. Anticipating this possibility, the Portuguese National Health Service carried out measures to prepare for this reality. This paper describes the changes implemented in the Anesthesiology department of a tertiary hospital center in Portugal, aiming to ensure the safety of both patients and healthcare professionals. The measures implemented had to do mostly with scientific preparation and team reorganization; management of personal protective equipment; redesigning the department's clinical common areas, separation of patient circuits with creation of a designated COVID Operating Room, Post-Anesthetic Care Unit; rescheduling of elective surgery and testing all patients before anesthesia procedures and consulting other hospital departments. The reported data covers the period between the 2nd March and the 30th April of 2020. In this period, 64 cases with COVID-19 or with high clinical suspicion were approached. To date, there have been no cases of in-hospital spread to other patients or to professionals in this department. With this paper we intend to start a reflection that will end up with the optimization of strategies that allows health systems to deal better with COVID-19, keeping patients and health providers safe.

Desde os primeiros casos de COVID-19 reportados pela República Popular da China, a 31 de dezembro de 2019, até à confirmação dos primeiros casos em Portugal, a 2 de março, países como Itália e Espanha depararam-se com o colapso dos seus sistemas de saúde. Antevendo essa possibilidade, o Serviço Nacional de Saúde preparou-se para enfrentar esta nova realidade. Neste documento descreve-se especificamente a preparação do serviço de Anestesiologia de um centro hospitalar terciário português, por forma a garantir a segurança dos seus doentes e profissionais de saúde. As medidas implementadas incidiram na preparação científica e reorganização das equipas; gestão do equipamento de proteção individual; reorganização dos espaços comuns do serviço; separação dos fluxos de doentes com a criação do Bloco Operatório e Unidade de Cuidados Pós-Anestésicos COVID; reprogramação da cirurgia eletiva; rastreio de todos os doentes propostos a procedimentos anestésicos e consultoria a outros serviços. Os dados apresentados compreendem a atividade desenvolvida entre 2 de março e 30 de abril de 2020. Nesse período foram abordados 64 casos com COVID-19 ou com elevada suspeita clínica, sendo que até à data não foram registados casos de contágio intra-hospitalar de outros doentes ou de profissionais neste serviço. Com este trabalho pretende-se iniciar uma reflexão que culmine numa futura otimização de estratégias que permitam aos serviços de saúde lidar com a COVID-19, mantendo a segurança dos outros doentes e dos profissionais de saúde.

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.

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

Atypical myeloproliferative neoplasm with concurrent BCR-ABL1 fusion and CALR mutation: A case report and literature review.

RATIONALE: Concurrent calreticulin (CALR) mutation and BCR-ABL1 fusion are extremely rare in chronic myelogenous leukemia; to date, only 12 cases have been reported. PATIENT CONCERNS: A 57-year-old male who had an 11-year history of essential thrombocytosis presented to our hospital with leukocytosis and marked splenomegaly for 3 months. DIAGNOSES: Chronic myelogenous leukemia with myeloid fibrosis arising on the background of essential thrombocytosis harboring both BCR-ABL1 fusion and type-1 like CALR mutation. INTERVENTIONS: Imatinib was started at 300 mg daily and increased to 400 mg daily after 3 months; interferon was added after 12 months. OUTCOMES: Partial cytogenetic response was achieved after 3 months of imatinib therapy and complete cytogenetic response was achieved after 1 year of treatment. However, CALR mutation was still present with a stable mutational allele burden. LESSONS: In this case report and review of additional 12 cases with simultaneous presence of CALR-mutation and BCR-ABL1 fusion, we highlighted the importance of integrating clinical, morphological, and molecular genetic data for classifying atypical myeloid neoplasms.

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.

Immunomodulatory effect of human bone marrow-derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a Th1/Th17-mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease-modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)-MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4+ and CD8+ T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM-MSCs. The expression of (interleukin) IL-2, tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) was evaluated in naive, central memory, effector memory, and effector CD4+ and CD8+ T cells, whereas IL-6, IL-9, and IL-17 expression was measured in total CD4+ and CD8+ T cells. mRNA expression of IL-4, IL-10, transforming growth factor beta (TGF-ß), cytotoxic T-lymphocyte-associated antigen 4, and/or forkhead box P3 was quantified in fluorescence-activated cell sorting-purified CD4+ T cells, CD8+ T cells, and CD4+ Treg. BM-MSCs inhibited the production of TNF-α, IL-17, IL-6, IL-2, IFN-γ, and IL-9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM-MSCs increased expression of IL-10 and TGF-ß by CD4+ and CD8+ T cells. BM-MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM-MSC-derived immunomodulation affected either naive, effector, and memory T cells.

Solid organ transplantation after hematopoietic stem cell transplantation in childhood: A multicentric retrospective survey.

We report data obtained from a retrospective multicenter pediatric survey on behalf of the European Society for Blood and Marrow Transplantation (EBMT). Information on solid organ transplantation (SOT) performed in pediatric recipients of either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) between 1984 and 2016 was collected in 20 pediatric EBMT Centers (25.6%). Overall, we evaluated data on 44 SOTs following HSCT including 20 liver (LTx), 12 lung (LuTx), 6 heart (HTx), and 6 kidney (KTx) transplantations. The indication for SOT was organ failure related to intractable graft-vs-host disease in 16 children (36.3%), acute or chronic HSCT-related toxicity in 18 (40.9%), and organ dysfunction related to the underlying disease in 10 (22.8%). The median follow-up was 10.9 years (95% confidence interval: 1.7-29.5). The overall survival rate at 1 and 5 years after SOT was 85.7% and 80.4%, respectively: it was 74% and 63.2% after LTx, 83.2% after HTx, and 100% equally after LuTx and KTx. This multicenter survey confirms that SOT represents a promising option in children with severe organ failure occurring after HSCT. Additional studies are needed to further establish the effectiveness of SOT after HSCT and to better understand the mechanism underlying this encouraging success.

Refractory Severe Thrombocytopenia during Pregnancy: How to Manage.

Thrombocytopenia is the most common hemostatic change in pregnancy, but severe thrombocytopenia is rare. One of the causes, immune thrombocytopenic purpura (ITP), is characterized by increased platelet destruction by immunoglobulin G (IgG) antibodies, presenting a high risk of hemorrhage for the patient, but also for the fetus, since antibodies may cross the placenta. We present the case of a 23-year-old pregnant woman with a history of Langerhans cell histiocytosis of the mandible submitted to surgery and chemotherapy when she was 10 years old, with diagnosis of ITP since then. At 28 weeks of gestation, she presented with petechiae, epistaxis, and gingival bleeding, with a platelet count of 3 × 109/L and positive IgG antiplatelet antibodies test. At a multidisciplinary discussion, it was decided to delay a cesarean section, due to the absence of fetal distress and to the high risk of morbidity for the patient. Many therapies were attempted without success. The IgG produced a slight and transient increase in the platelet count. On the 36th week of gestation, an elective cesarean section was performed. The perioperative period transfusions were guided by rotational thromboelastometry (ROTEM) monitoring. The procedure was performed under general anesthesia and videolaryngoscopy-assisted intubation. The patient was hemodynamically stable, without significant bleeding, and was transferred to the intensive care unit. The platelet count eventually decreased and a splenectomy was performed. Regional anesthesia may be contraindicated, and general anesthesia is associated with an increased risk of airway hemorrhage due to traumatic injury during the tracheal intubation and of hemorrhage associated with the surgical procedure. A multidisciplinary approach is essential in high-risk cases.

A trombocitopenia é a alteração da hemostase mais comum na gravidez. Contudo, a trombocitopenia grave é rara. Uma das suas causas, a púrpura trombocitopênica imunológica (PTI), é caracterizada pelo aumento da destruição plaquetária por anticorpos de imunoglobulina G (IgG), apresentando alto risco de hemorragia para a paciente e também para o feto, uma vez que os anticorpos podem atravessar a placenta. Apresentamos o caso de uma grávida de 23 anos com histórico de histiocitose de células de Langerhans da mandíbula submetida a cirurgia e quimioterapia aos 10 anos de idade, com diagnóstico de PTI desde então. Na 28a semana de gestação, a paciente apresentou um quadro de petéquias, epistaxe e hemorragia gengival, com contagem plaquetária de 3 × 109/L e teste de anticorpos antiplaquetários IgG positivo. Em uma discussão multidisciplinar, decidiu-se adiar a cesariana devido à ausência de sofrimento fetal e ao alto risco de morbidade para a paciente. Muitas terapêuticas foram tentadas sem sucesso. A IgG produziu apenas um ligeiro e transitório aumento na contagem plaquetária. Na 36ª semana de gestação, foi realizada uma cesariana eletiva. As transfusões no período perioperatório foram guiadas por tromboelastometria rotacional (ROTEM). O procedimento foi realizado sob anestesia geral e intubação assistida por videolaringoscopia. A paciente manteve-se hemodinamicamente estável, sem hemorragia significativa. Ela foi transferida para a unidade de terapia intensiva. A contagem plaquetária continuou a diminuir, e a paciente foi submetida a uma esplenectomia. Nestes casos, a anestesia regional pode ser contraindicada, e a anestesia geral está associada a um risco aumentado de hemorragia das via aéreas devido a lesão traumática durante a intubação traqueal e de hemorragia associada ao procedimento cirúrgico. Uma abordagem multidisciplinar é essencial em casos de alto risco.

Refractory severe thrombocytopenia during pregnancy: how to manage / Trombocitopenia grave refratária na gravidez: como abordar

Abstract Thrombocytopenia is the most common hemostatic change in pregnancy, but severe thrombocytopenia is rare. One of the causes, immune thrombocytopenic purpura (ITP), is characterized by increased platelet destruction by immunoglobulin G (IgG) antibodies, presenting a high risk of hemorrhage for the patient, but also for the fetus, since antibodiesmay cross the placenta.We present the case of a 23-year-old pregnant woman with a history of Langerhans cell histiocytosis of the mandible submitted to surgery and chemotherapy when she was 10 years old, with diagnosis of ITP since then. At 28 weeks of gestation, she presented with petechiae, epistaxis, and gingival bleeding, with a platelet count of 3 x 109/L and positive IgG antiplatelet antibodies test. At a multidisciplinary discussion, it was decided to delay a cesarean section, due to the absence of fetal distress and to the high risk of morbidity for the patient. Many therapies were attempted without success. The IgG produced a slight and transient increase in the platelet count. On the 36th week of gestation, an elective cesarean section was performed. The perioperative period transfusions were guided by rotational thromboelastometry (ROTEM) monitoring. The procedure was performed under general anesthesia and videolaryngoscopy-assisted intubation. The patient was hemodynamically stable, without significant bleeding, and was transferred to the intensive care unit. The platelet count eventually decreased and a splenectomy was performed. Regional anesthesia may be contraindicated, and general anesthesia is associated with an increased risk of airway hemorrhage due to traumatic injury during the tracheal intubation and of hemorrhage associated with the surgical procedure. A multidisciplinary approach is essential in high-risk cases.

Resumo A trombocitopenia é a alteração da hemostase mais comum na gravidez. Contudo, a trombocitopenia grave é rara. Uma das suas causas, a púrpura trombocitopênica imunológica (PTI), é caracterizada pelo aumento da destruição plaquetária por anticorpos de imunoglobulina G (IgG), apresentando alto risco de hemorragia para a paciente e também para o feto, uma vez que os anticorpos podem atravessar a placenta. Apresentamos o caso de uma grávida de 23 anos com histórico de histiocitose de células de Langerhans da mandíbula submetida a cirurgia e quimioterapia aos 10 anos de idade, com diagnóstico de PTI desde então. Na 28a semana de gestação, a paciente apresentou um quadro de petéquias, epistaxe e hemorragia gengival, com contagem plaquetária de 3 x 109/L e teste de anticorpos antiplaquetários IgG positivo. Em uma discussão multidisciplinar, decidiu-se adiar a cesariana devido à ausência de sofrimento fetal e ao alto risco de morbidade para a paciente. Muitas terapêuticas foram tentadas sem sucesso. A IgG produziu apenas um ligeiro e transitório aumento na contagem plaquetária. Na 36ª semana de gestação, foi realizada uma cesariana eletiva. As transfusões no período perioperatório foram guiadas por tromboelastometria rotacional (ROTEM). O procedimento foi realizado sob anestesia geral e intubação assistida por videolaringoscopia. A paciente manteve-se hemodinamicamente estável, sem hemorragia significativa. Ela foi transferida para a unidade de terapia intensiva. A contagem plaquetária continuou a diminuir, e a paciente foi submetida a uma esplenectomia. Nestes casos, a anestesia regional pode ser contraindicada, e a anestesia geral está associada a um risco aumentado de hemorragia das via aéreas devido a lesão traumática durante a intubação traqueal e de hemorragia associada ao procedimento cirúrgico. Uma abordagem multidisciplinar é essencial em casos de alto risco.

Outcomes of Advanced Hodgkin Lymphoma after Umbilical Cord Blood Transplantation: A Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party Study.

Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL), but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in European Society for Blood and Marrow Transplantation centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 patients (47%), and almost all patients had received a previous autologous stem cell transplantation. The 4-year progression-free survival (PFS) and overall survival (OS) were 26% (95% confidence interval [CI], 19% to 34%) and 46% (95% CI, 37% to 55%), respectively. Relapse incidence was 44% (95% CI, 36% to 54%), and nonrelapse mortality (NRM) was 31% (95% CI, 23% to 40%) at 4 years. In multivariate analysis refractory/relapsed disease status at UCBT was associated with increased relapse incidence (hazard ratio [HR], 3.14 [95% CI, 1.41 to 7.00], P = .005) and NRM (HR, 3.61 [95% CI, 1.58 to 8.27], P = .002) and lower PFS (HR, 3.45 [95% CI, 1.95 to 6.10], P < .001) and OS (HR, 3.10 [95% CI, 1.60 to 5.99], P = .001). Conditioning regimen with cyclophosphamide + fludarabine + 2 Gy total body irradiation (Cy+Flu+2GyTBI) was associated with decreased risk of NRM (HR, .26 [95% CI, .10 to .64], P = .004). Moreover, Cy+Flu+2GyTBI conditioning regimen was associated with a better OS (HR, .25 [95% CI, .12 to .50], P < .001) and PFS (HR, .51 [95% CI, .27 to .96], P = .04). UCBT is feasible in heavily pretreated patients with HL. The reduced-intensity conditioning regimen with Cy+Flu+2GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT.

Unrelated Cord Blood Transplantation for Acute Leukemia Diagnosed in the First Year of Life: Outcomes and Risk Factor Analysis.

Infant acute leukemia still has a poor prognosis, and allogeneic hematopoietic stem cell transplantation is indicated in selected patients. Umbilical cord blood (UCB) is an attractive cell source for this population because of the low risk of chronic graft-versus-host disease (GVHD), the strong graft-versus-leukemia effect, and prompt donor availability. This retrospective, registry-based study reported UCB transplantation (UCBT) outcomes in 252 children with acute lymphoblastic leukemia (ALL; n = 157) or acute myelogenous leukemia (AML; n = 95) diagnosed before 1 year of age who received a single-unit UCBT after myeloablative conditioning between 1996 and 2012 in European Society for Blood and Marrow Transplantation centers. Median age at UCBT was 1.1 years, and median follow-up was 42 months. Most patients (57%) received a graft with 1 HLA disparity and were transplanted in first complete remission (CR; 55%). Cumulative incidence function (CIF) of day 100 acute GVHD (grades II to IV) was 40% ± 3% and of 4-year chronic GVHD was 13% ± 2%. CIF of 1-year transplant-related mortality was 23% ± 3% and of 4-year relapse was 27% ± 3%. Leukemia-free-survival (LFS) at 4 years was 50% ± 3%; it was 40% and 66% for those transplanted for ALL and AML, respectively (P = .001). LFS was better for patients transplanted in first CR, regardless of diagnosis. In multivariate model, diagnosis of ALL (P = .001), advanced disease status at UCBT (<.001), age at diagnosis younger than 3 months (P = .012), and date of transplant before 2004 were independently associated with worse LFS. UCBT is a suitable option for patients diagnosed with infant acute leukemia who achieve CR. In this cohort, patients with AML had better survival than those with ALL.

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Median age at UCBT was 6 months. Seventy-seven percent of the cord blood grafts had 0 or 1 HLA disparity with the recipient. Conditioning regimen was myeloablative (mostly busulfan-based in 84% and treosulfan-based in 10%). Antithymocyte globulin was given to 90% of patients. Median number of total nucleated and CD34+ cells infused was 14 × 107/kg and 3.4 × 105/kg, respectively. Median follow-up for survivors was 74 months. Cumulative incidence (CI) of neutrophil recovery was 67% with a median time to recovery of 23 days; 33% of patients had graft failure, 81% of engrafted patients had full donor engraftment, and 19% had mixed donor chimerism. Day 100 CI of acute graft-versus-host disease (grades II to IV) was 31% and 6-year CI of chronic graft-versus-host disease was 21%. Mechanical ventilation was required in 28%, and veno-occlusive disease was diagnosed in 16% of cases. Six-year overall survival rate was 46%. Comparative studies with other alternative donors should be performed to evaluate whether UCBT remains a valid alternative for children with OP without an HLA-matched donor.