Fungal infections in hematopoietic stem cell transplantation in children at a pediatric children's hospital in Argentina.

Our primary objective was to describe the incidence of proven or probable invasive fungal infections (IFIs), a devastating complication of hematopoietic stem cell transplant (HSCT), in HCST in a middle-income country. Secondary objectives were to describe factors associated with IFIs and outcomes. In this single center retrospective study, pediatric patients who underwent a first allogeneic or autologous HSCT from 1998 to 2016 were included. Of the 251 HSCT recipients: 143 transplants were allogeneic and 108 were autologous. Overall, 23 (9%) experienced an IFI, mostly due to yeasts (83%). IFIs were more common in allogeneic HSCT (18/143, 13%) than in autologous HSCT (5/108, 5%; P = .045). Of the 23 patients with IFIs, 14 (61%) died, but only 1 directly from IFI (pulmonary aspergillosis). Overall survival at 3 years was 0.42 ± 0.11 in patients with IFIs and 0.60 ± 0.37 in those without IFIs (P = .049). In Argentina, IFIs during HSCT are common. Recipients of allogeneic HSCT are at higher risk, and IFI is associated with reduced overall survival. Future work should focus on interventions to reduce and improve IFI outcomes in children undergoing transplants in low- and middle-income countries.

Ajuste de intensidad para el trasplante hematopoyético alogénico en leucemia aguda / Intensity adjustment of hematopoietic alogeneic transplantation in acute leukemia

Background: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. Aim: To report our experience with HSCT in patients of different ages with acute leukemia. Material and Methods: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. Results: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. Conclusions: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.

[Intensity adjustment of hematopoietic alogeneic transplantation in acute leukemia]. / Ajuste de intensidad para el trasplante hematopoyético alogénico en leucemia aguda.

BACKGROUND: The intensity of conditioning chemotherapy and radiotherapy in hematopoietic stem cell transplantation (HSCT) varies according to several factors including the patient’s age, pre-existing conditions and performance status. Myeloablative conditioning (MA) increases transplant related mortality and reduces survival in older patients. Reduced intensity conditioning (RIC) is a good option for these patients. AIM: To report our experience with HSCT in patients of different ages with acute leukemia. MATERIAL AND METHODS: Retrospective analysis of 115 allogeneic HSCT performed in patients with acute myeloid or lymphoblastic leukemia. RESULTS: We analyzed the cohort of patients in groups according to age at transplantation: younger than 40 years (n = 74), 41 to 50 years (n = 25) and older than 51 years of age (n = 16). Overall survival (OS), Disease free survival (DFS) and relapse at five years were similar in both groups of patients younger than 50 years (OS 40 and 44% respectively, DFS 38 and 42% respectively and relapse 40% and 34% respectively, p = NS). Patients over 51 years had a five years OS of 12%. However when we analyzed those patients by date and conditioning we found that patients who were treated with MA regimens in the first decade of the transplant program (before 2000) had lower OS compared to those treated after 2000 with RIC (five years OS 49% and 12% respectively, p < 0.01). No significant differences in terms of OS, recurrence or incidence of graft-versus-host disease were found when comparing groups under 40 years, between 41 and 50 years and older than 51 years treated only with RIC. CONCLUSIONS: RIC provides the possibility of HSCT in older patients with rates comparable to those obtained in younger patients successfully treated with MA conditioning.

Assessment of the outcomes associated with periprocedural anticoagulation management in children with acute lymphoblastic leukemia.

OBJECTIVE: To report the outcomes of an institutional protocol for periprocedural anticoagulant (AC) management in children with acute lymphoblastic leukemia (ALL). STUDY DESIGN: Children being treated for ALL who received full-dose (therapeutic) anticoagulation before undergoing at least 1 lumbar puncture (LP) were included in this retrospective cohort study. The main outcome was the risk of traumatic LP; exploratory analysis included the risks of symptomatic spinal hematoma and progression/recurrence of the thrombotic event. Analyses were conducted using logistic regression analysis with a generalized estimating equation approach. RESULTS: Twenty-two children with ALL receiving an AC underwent a total of 396 LPs. Although traumatic LP was associated with full-dose AC therapy in univariable analysis, a multiple logistic regression model controlling for other risk factors for traumatic LP showed that AC therapy was not significantly associated with the risk of traumatic LP when the ACs were held as per the institutional protocol. No patient developed symptomatic spinal hematoma. Exploratory analysis revealed that AC dose, a likely marker of thrombus burden, was significantly associated with progression/recurrence of the thrombotic event in univariable analysis. CONCLUSION: In our cohort, recent AC therapy was not statistically associated with an increased risk of bleeding after LP when following a specific protocol for periprocedural AC management. The risk associated with the progression/recurrence of thromboembolic events requires further evaluation.

Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002.

PURPOSE: From 2002 to 2007, the International Berlin-Frankfurt-Münster Study Group conducted a prospective randomized clinical trial (ALL IC-BFM 2002) for the management of childhood acute lymphoblastic leukemia (ALL) in 15 countries on three continents. The aim of this trial was to explore the impact of differential delayed intensification (DI) on outcome in all risk groups. PATIENTS AND METHODS: For this trial, 5,060 eligible patients were divided into three risk groups according to age, WBC, early treatment response, and unfavorable genetic aberrations. DI was randomized as follows: standard risk (SR), two 4-week intensive elements (protocol III) versus one 7-week protocol II; intermediate risk (IR), protocol III × 3 versus protocol II × 1; high risk (HR), protocol III × 3 versus either protocol II × 2 (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP] option), or 3 HR blocks plus single protocol II (Berlin-Frankfurt-Münster [BFM] option). RESULTS: At 5 years, the probabilities of event-free survival and survival were 74% (± 1%) and 82% (± 1%) for all 5,060 eligible patients, 81% and 90% for the SR (n = 1,564), 75% and 83% for the IR (n = 2,650), and 55% and 62% for the HR (n = 846) groups, respectively. No improvement was accomplished by more intense and/or prolonged DI. CONCLUSION: The ALL IC-BFM 2002 trial is a good example of international collaboration in pediatric oncology. A wide platform of countries able to run randomized studies in ALL has been established. Although the alternative DI did not improve outcome compared with standard treatment and the overall results are worse than those achieved by longer established leukemia groups, the national results have generally improved.

Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón / Allogenic hematopoietic stem cell transplantation with unrelated cord blood: Report of three cases from the Chilean cord blood bank

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

[Mycobacterium tuberculosis infection in a pediatric patient who underwent a hematopoietic stem cell transplant]. / Infección por Mycobacterium tuberculosis en una niña sometida a trasplante de progenitores hematopoyéticos.

We report the case of a 10 year old girl with a relapsed acute lymphoblastic leukemia, who underwent a haploidentical hematopoietic stem cell transplant (HSCT), with grade II skin and digestive graft versus host disease, treated with corticosteroids and cyclosporine. On day + 54, she presented fever, with no other remarkable clinical findings. Imaging study showed the presence of lung and liver nodules, liver biopsy was performed. The study included histology, staining and culture for bacteria and fungi, and the preservation of a piece of tissue at -20°C for future prospective studies. Ziehl Nielsen stain was positive, and study for Mycobacterium infection was performed. Microbiological smears of tracheal and gastric aspirate, and bronchial fluid obtained by bronchoalveolar lavage (BAL) were positive. The final report confirmed Mycobacterium tuberculosis in gastric content, sputum, BAL and liver tissue, susceptible to rifampin, isoniazid, streptomycin and ethambutol, with determination of mutations for genes rpoß and kat G (-). Tuberculosis (TB) diagnosis was confirmed. The girl received daily therapy for two months and then she continued on three times per week therapy for 9 months. Controlled by the transplant, infectious diseases and respiratory teams, the patient remained in good general condition, with radiologic resolution of pulmonary and liver involvement and negative smears. We conclude that Mycobacterium tuberculosis infection should be part of differential diagnosis of febrile illness in patients undergoing HSCT, and biopsy should be a standard practice of early diagnosis in these patients.

Infección por Mycobacterium tuberculosis en una niña sometida a trasplante de progenitores hematopoyéticos / Mycobacterium tuberculosis infection in a pediatric patient who underwent a hematopoietic stem cell transplant

We report the case of a 10 year old girl with a relapsed acute lymphoblastic leukemia, who underwent a haploidentical hematopoietic stem cell transplant (HSCT), with grade II skin and digestive graft versus host disease, treated with corticosteroids and cyclosporine. On day + 54, she presented fever, with no other remarkable clinical findings. Imaging study showed the presence of lung and liver nodules, liver biopsy was performed. The study included histology, staining and culture for bacteria and fungi, and the preservation of a piece of tissue at -20°C for future prospective studies. Ziehl Nielsen stain was positive, and study for Mycobacterium infection was performed. Microbiological smears of tracheal and gastric aspirate, and bronchial fluid obtained by bronchoalveolar lavage (BAL) were positive. The final report confirmed Mycobacterium tuberculosis in gastric content, sputum, BAL and liver tissue, susceptible to rifampin, isoniazid, streptomycin and ethambutol, with determination of mutations for genes rpoβ and kat G (-). Tuberculosis (TB) diagnosis was confirmed. The girl received daily therapy for two months and then she continued on three times per week therapy for 9 months. Controlled by the transplant, infectious diseases and respiratory teams, the patient remained in good general condition, with radiologic resolution of pulmonary and liver involvement and negative smears. We conclude that Mycobacterium tuberculosis infection should be part of differential diagnosis of febrile illness in patients undergoing HSCT, and biopsy should be a standard practice of early diagnosis in these patients.

Se presenta el caso clínico de una niña de 10 años, con una leucemia linfoblástica aguda en recaída, sometida a un trasplante de progenitores hematopoyéticos (TPH) haploidéntico, con enfermedad injerto contra hospedero cutánea y digestiva grado II, en tratamiento con corti-costeroides y ciclosporina, que presentó el día +54 posttrasplante fiebre y compromiso de estado general. Dentro del estudio de su cuadro febril se practicaron imágenes que mostraron presencia de nódulos pulmonares y hepáticos. Se realizó una biopsia hepática cuyo estudio incluyó histología, tinciones y cultivo para bacterias y hongos. La tinción de Ziehl Nielsen de tejido hepático, así como las baciloscopias de contenido gástrico, aspirado traqueal y de fluido bronquial obtenido por lavado broncoalveolar (LBA) fueron positivas. El informe definitivo de cultivo confirmó Mycobacterium tuberculosis en contenido gástrico, esputo, LBA y tejido hepático, sensible a rifampicina, isoniazida, estreptomicina y etambutol, con determinación de mutaciones de genes rpoβ y kat G (-). Se confirmó el diagnóstico de tuberculosis, por lo que recibió tratamiento diario con cuatro fármacos por dos meses y luego terapia trisemanal con rifampicina, isoniazida y etambutol por nueve meses. Controlada por los equipos de trasplante, infectología y broncopulmonar, la paciente se mantiene actualmente en buenas condiciones generales, con imágenes con resolución del compromiso hepático y pulmonar y baciloscopias negativas. La infección por M. tuberculosis debe formar parte del diagnóstico diferencial de los cuadros febriles en los pacientes sometidos a TPH, y la toma de biopsia debe ser una práctica habitual y precoz en el enfrentamiento diagnóstico de estos pacientes.

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank]. / Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón.

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Cirrhosis due to chronic hepatitis E infection in a child post-bone marrow transplant.

Chronic hepatitis E virus (HEV) infection occurs in immunosuppressed adults. We detected HEV ribonucleic acid in serum of an adolescent patient who had undergone bone marrow transplantation and subsequently presented with persistently increased aminotransferases and histologic chronic hepatitis, and eventually developed cirrhosis. Phylogenetic analysis revealed these HEV strains were similar to swine genotype 3a, suggesting a possible zoonosis.

Imatinib-associated hyperpigmentation of the palate in post-HSCT patient.

Pigmentation of the oral mucosa can indicate a wide range of lesions or conditions. Some drugs are associated with pigmented lesions of oral cavity. Imatinib mesylate (Gleevec(®)) is a protein inhibitor used in the management of several hematological malignancies associated with dermatological side effects, like hyperpigmentation. We report the case of a 38-year-old male post-HSCT patient who had been using imatinib mesylate for over 5 years and presented with blue pigmentation on the hard palate, the left side of the nose and both ear lobes. The differential diagnosis of hyperpigmented lesions in the oral mucosa is also presented.

Linfoma linfoblástico tipo Burkitt dos ovários / Burkitt's lymphoblastic lymphoma of the ovaries

Os autores realatam um caso de comprometimento bilateral dos ovários por linfoma linfoblástico tipo Burkitt em uma paciente de 14 anos. De acordo com a revisao bibliográfica o ovário é o segundo sítio mais comum de linfoma de Burkitt depois da mandíbula.

Total lymphoid irradiation for treatment of drug resistant chronic GVHD.

We report our experience with total lymphoid irradiation (TLI) in three patients with GVHD which had failed to respond to standard drug treatment. The clinical manifestations of GVHD markedly improved with TLI treatment.

Growth in children after bone marrow transplantation for advanced neuroblastoma compared with growth after transplantation for leukemia or aplastic anemia.

The linear growth of 26 children with progressive and advanced neuroblastoma treated with high-dose chemotherapy, total body irradiation, and bone marrow transplantation between 1978 and 1988 at the Children's Hospital of Philadelphia was compared with the growth of 33 children who had transplants for leukemia and of 12 who had transplants for aplastic anemia. The mean growth velocity, expressed as a standard deviation score, for the children who underwent bone marrow transplantation for neuroblastoma was -2.83. This was significantly (p less than 0.005) less than the standard deviation scores for children with transplants for acute lymphoblastic leukemia, acute nonlymphocytic leukemia, and aplastic anemia, which were -0.98, -0.07, and -1.05, respectively. A 6-year follow-up study of 32 long-term survivors of cancer revealed that the 11 patients with neuroblastoma continued to grow poorly, whereas a comparison group of 21 survivors of bone marrow transplantation for leukemia had essentially normal growth 2 years after the procedure. Major therapeutic differences between the two groups included the doses of local radiotherapy and the type and number of cytotoxic agents used. In comparison with the relatively mild growth-inhibiting effects of preparative regimens for leukemia and aplastic anemia, the very intensive preparative regimens used in patients with neuroblastoma have significant negative effects on growth.

Abdomen agudo como forma de presentación de leucemia aguda / Acute abdomen as the first sympton of acute leukemia

Dentro de la sintomatología inicial, el dolor abdominal está presente aproximadamente en casi un 7 por ciento de los pacientes con leucemia. Es poco frecuente que el comienzo de la enfermedad presente un cuadro de apendicitis aguda. Se describen 2 pacientes, una niña de 9 años con leucemia mieloide aguda que se trató médicamente y un varón de 3 años con leucemia linfoide aguda que requirió intervención quirúrgica hallándose una apendicitis gangrenosa retrocecal. Sugerimos, como conclusiones, que ante un síndrome de fosa ilíaca derecha con marcada leucopenia y neutropenia se tenga en cuenta el diagnóstico de esta enfermedad hematológica y que una vez hecho éste, si la conducta quirúrgica está indicada, se lleve a cabo sin demora, en beneficio del pronóstico de estos enfermos.

Bone marrow transplantation for acute leukemia and Down syndrome: report of a successful case and results of a national survey.

We report a child with Down syndrome (DS) and acute lymphoblastic leukemia who is a healthy survivor 38 months after bone marrow transplantation (BMT). Psychometric evaluations performed before and after BMT indicate no demonstrable therapy-related change in intellectual function. A survey of BMT centers in the United States indicated that 16 leukemic DS children have had transplants at 10 BMT centers. Seven of these children survive at 11, 14, 17, 18, 22, 38, and 47 months, respectively, after BMT. Although these results are comparable to those for non-DS children, the number of DS children having transplants is only 20% to 25% of that predicted. We conclude that there is no justification for denial of BMT to otherwise appropriate candidates with DS and leukemia.