Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study.

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

Respiratory Viral Infections in the Pediatric Hematopoietic Stem Cell Transplant Population: Progression to Lower Respiratory Tract Disease.

BACKGROUND: Respiratory viral infections (RVIs) are important complications in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT); however, risk factors for lower respiratory tract infections (LRTIs) are not well characterized. The aim of this study was to determine risk factors for the progression to LRTIs in pediatric patients with respiratory symptoms who underwent HSCT. PATIENTS AND METHODS: This retrospective study included 87 pediatric patients with respiratory symptoms who underwent HSCT. Respiratory viral polymerase chain reaction samples were obtained from all patients. The evaluated data included risk factors to progression to LRTIs, long-term pulmonary complications, transplantation-related mortality, and overall survival. RESULTS: Viral pathogens were detected in 31 (48.4%) patients with upper respiratory tract infections and 13 (56.5%) patients with LRTIs. There was a statistically significant difference between the groups in engraftment delay and lymphocytopenia. Also it was determined that engraftment delay (odds ratio: 7.46 [95% CI, 1.99 to 27.86]; P = 0.003) and COVID-19 infection had statistically significant effects on overall survival in general (odds ratio: 8.06 [95% CI, 2.63 to 24.64]; P <0.001]). CONCLUSION: Not only host and transplant-related factors but also viral agent type were found to be effective in progression to LRTIs. As the available therapy for respiratory viral infections remains limited, the focus should be on the prevention of infection.

The Impact of Panel Reactive Antibodies and Different Desensitization Methods on Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Outcomes.

INTRODUCTION: In highly sensitized patients who have panel reactive antibodies (PRAs) before hematopoietic stem cell transplantation, primary graft failure risk may increase. In this study, we aimed to determine the association of PRA with engraftment, and graft versus host disease (GVHD) in pediatric patients. MATERIALS AND METHODS: Forty-three PRA-positive and 42 PRA-negative patients were taken into study. Both groups were compared in terms of graft failure, acute GVHD, viral infection and survival rates. PRA-positive group was also divided into 2 according to treatment modality (steroid-only group/combination therapy) and compared for the same parameters. RESULTS: There was no difference in PRA-positive and negative patients in terms of graft failure, acute GVHD and viral infections. Analysis of the PRA-positive group in itself showed that there was also no difference in terms of graft failure and viral infection frequency. The only difference is that acute grade 3 to 4 GVHD was higher in the steroid-only group. The 100-day overall survival was 90.2% and 90.4% for the PRA-positive and negative groups, respectively. CONCLUSIONS: Different treatment strategies like plasmapheresis, steroid, rituximab, or combination therapies can be used for the desensitization of PRA-positive patients before hematopoietic stem cell transplantation. Patient-specific treatment modality for sensitized patients before transplant can increase the success rate.

Co-transplantation of mesenchymal stromal cell and haploidentical hematopoietic stem cell with TCR αß depletion in children with primary immunodeficiency syndromes.

BACKGROUND: Haploidentical HSCT is a good option for children with PIDs lacking an HLA-matched donor. Co-transplantation of MSCs during haploidentical HSCT in patients with PIDs may enhance engraftment, decrease the risk of GVHD, and ensure stable donor chimerism. METHODS: Twenty-seven pediatric patients (median age, 1.4 years; range, .3-10.9) with PIDs undergoing thirty haploidentical HSCT with TCR αß depletion and co-transplantation of MSCs were enrolled to study. Most patients (73.3%) received myeloablative conditioning consisting of treosulfan or busulfan, fludarabine, and thiotepa. The median duration of follow-up was 14.3 months (range, 1-69 months). RESULTS: Acute GVHD occurred in 7 patients (grade I-II n = 5, grade III-IV n = 2). Chronic GVHD was observed in only one patient. Twenty-one patients (70.2%) had 100% donor chimerism in all cell lines including T-cell and B-cell lineages. Primary graft failure was observed in 7 patients (25.9%). The cumulative incidences of TRM were 20% at day 100, and 26.7% at one year and five years. Probabilities of OS were 80% at day 100, and 71.9% at 1 year and 5 years. Infants transplanted younger than 6 months of age had the highest 5-year survival rate (85.7%). CONCLUSION: We conclude that use of TCR αß depleted haploidentical transplantation with MSCs may ensure a rapid engraftment rate, low incidence of significant acute and chronic GVHD, and acceptable post-transplantation morbidity, especially in patients diagnosed with SCID and may be considered in children with PIDs. In younger patients (≤6 months), survival is comparable between HLA-matched graft and CD3+ TCRαß depleted HLA-mismatched graft recipients.

Clinical study of graft-versus-host disease prophylaxis in unrelated hematopoietic stem cell transplantation for pediatric nonmalignant diseases with different doses anti-human T-lymphocyte immunoglobulin.

BACKGROUND: Anti-human T-lymphocyte immunoglobulin is commonly used as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors. The studies according to optimum dose of ATLG especially in pediatric patients are limited. PATIENTS AND METHODS: Outcomes of 99 pediatric patients diagnosed with nonmalignant diseases, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2), and 30 mg/kg (group 3), were analyzed retrospectively. RESULTS: The incidences of acute and chronic GVHD were statistically not different between three groups (p = .20 and p = .13), but we did not observe chronic GVHD in group 3 patients. Cox regression analysis showed that ATLG dose of 10 mg/kg (p = .007) and severe acute GVHD (p = .001) were significant prognostic factors for inferior overall survival. Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention, TRM and overall survival were superior in ATLG doses ≥20 mg/kg (p = .04 and p = .037) with no difference between 20 and 30 mg/kg. CONCLUSION: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection, TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 and 30 mg/kg. These observations should be supported with other multicenter prospective studies including larger patient population.

Management of a Patient With Congenital Biallelic CSF3R Mutation With GM-CSF.

Severe Congenital Neutropenia (SCN) is a rare inherited disease characterized by an absolute neutrophil count (ANC) lower than 500/µL. Genetic heterogeneity and biallelic CSF3R mutation has rarely been identified as an underlying genetic defect in SCN. The majority of SCN patients respond to granulocyte colony stimulating factor treatment; however, in patients with inherited CSF3R mutation, ANC cannot generally be increased with granulocyte colony stimulating factor treatment. In such cases, granulocyte macrophage colony stimulating factor presents as an effective treatment option. Herein, we report a case of a 5-year-old SCN girl with homozygous c610-611 del ins AG (p.Q204R) mutation in the CSF3R gene, who was successfully treated with granulocyte macrophage colony stimulating factor.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry.

BACKGROUND: Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. METHOD: Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. RESULTS: The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow-up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. CONCLUSION: In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.

Congenital Neutropenia Patient With Hypomorphic Biallelic CSF3R Mutation Responding to GCSF.

Congenital neutropenia (CN) is a rare disorder, and the most common gene responsible for CN is ELANE. Furthermore, the mutations of HAX1, G6PC3, and JAGN1 genes may cause CN. These patients generally find great benefit from subcutaneous administration of Granulocyte Colony Stimulating Factor (GCSF). In recent years, Biallelic Colony Stimulating Factor 3 Receptor (CSF3R) mutations have been described as an underlying defect of CN in several children. In contrast to the previous group, the patients who have a CSF3R mutation do not respond to GCSF treatment. Here, we present a CN patient with hypomorphic biallelic CSF3R mutation responding to GCSF.

Inferior Petrosal Sinus Thrombosis in a Child due to Malposition of Central Venous Catheter: A Case Report.

OBJECTIVE: To report a case of inferior petrosal sinus thrombosis associated with malposition of central venous catheterization (CVC). CLINICAL PRESENTATION AND INTERVENTION: A 5-month-old boy was admitted to Sifa University Hospital because of pneumonia. When exophthalmos occurred in the right eye, he was referred to Ege University Hospital. Cranial magnetic resonance imaging and magnetic resonance venography confirmed that the catheter in the right inferior petrosal sinus caused the thrombosis. The catheter was extracted and anticoagulant treatment was started. CONCLUSION: In this case report, malpositioning of the CVC was the cause of the thrombosis. To minimize such complications, catheterization should be done with the supervision of an expert and postprocedure radiography should also be performed.

Fatal disseminated Magnusiomyces clavatus infection with rash in pediatric acute lymphoblastic leukemia: A case report.

Magnusiomyces clavatus is a rare yeast-like fungus that can cause opportunistic infections in immunocompromised patients. Here, we present a 14-year-old patient who was followed up with the diagnosis of acute lymphoblastic leukemia, developed skin rashes, and Magnusiomyces clavatus infection detected. The patient died shortly after the infection was diagnosed.

How effective is reducing traffic speed for safer work zones? Methodology and a case study in Pennsylvania.

Transportation agencies post and enforce reduced speed limits in work zones to ensure work zone safety, since traffic speed is found to be associated with work zone crash risks. However, prior findings on the relationship between speed and crash rate in work zones are inconsistent. This may be attributed to the methods of statistical associations between traffic speed and crash risks that do not necessarily discover true causal relations. In fact, work zone presence could lead to the reduction of actual traffic speed that influences crash risks, where it may also directly impose effects on crash risks as a result of work zone configurations. The actual traffic speed (not posted speed limit) is also known as a "mediator" where work zones can indirectly impact the crash risks. It is challenging to rigorously separate the causal effect of traffic speed on work zone crash risk from that directly caused by work zones. The underlying causal relation could help to determine what reduced post speed limit (with enforcement) is necessary to ensure work zone safety under the most desired "actual traffic speed". This study proposes to use the sequential g-estimation and the regression discontinuity design to estimate the controlled direct effect of traffic speed on work zone crashes. Two research gaps are identified and filled: inaccurate inferences of the effect of reduced speed limit in work zones as a result of ignoring (1) potential post-treatment bias since traffic speed is a mediator; and (2) potential confounding bias caused by unobservable roadway characteristics. The proposed methodology was applied to 4008 work zones in Pennsylvania from 2015 to 2017, and the results were validated through a series of robustness tests. The results indicate that the direct causal effect of the presence of work zones on crash risk is significantly positive when the traffic speed is relatively low (i.e., lower than 55 mph in this case study), while traffic speed has a positive causal effect on crash occurrences when the actual traffic speed is high (i.e., greater or equal to 55 mph). It suggests that strictly enforcing reduced posted speed limits in work zones is particularly effective when the actual traffic speed is greater than 55 mph. This is particularly true on roadways with high traffic volume (i.e., AADT > 20,000 vehicles per day), long, and daytime work zones (i.e., > 3000 m). On the other hand, the effect of enforcing reduced speed on work zone safety is unclear when the actual speed is already low. In this case, improving work zone configurations and driving behaviors may be more effective in reducing crash risks.

Inferring heterogeneous treatment effects of work zones on crashes.

The increasing number of work zone crashes has been a significant concern for road users, transportation agencies, and researchers. Crashes can be caused by work zones, and this effect changes across different work zone configurations, traffic volumes, roadway functional classifications, and weather conditions. This is typically represented by Crash Modification Functions (CMFunctions). However, current methods for developing work zone CMFunctions have two major limitations: (1) They focus on analyzing statistical associations and fail to mitigate the confounding bias due to possible unobservable roadway characteristics; and (2) They cannot address CMFunctions of multiple variables simultaneously, such as weather and traffic conditions, since they are represented using mixed data types (continuous and categorical) that could potentially affect the causal effect of work zones on crashes. In this study, we develop a method that utilizes causal forest with fixed-effect modeling to mitigate the confounding bias while identifying CMFunctions conditioning on various environmental characteristics, including work zone configurations, traffic volume, roadway functional classification, and weather conditions. The developed method was applied to 3378 work zones that occurred in Pennsylvania between 2015 and 2017. The results were validated via a series of robustness tests. The validations demonstrate that this method can mitigate the confounding bias and identify CMFunctions of multiple variables. The results also show that the causal effect of a work zone on crash occurrence is significantly positive (p<0.05) on roadways with high traffic volumes (e.g., > 20,000 vehicles per day) and on medium length (e.g., 2000 to 5000 m) work zones. It appears that having medium-long (e.g., between 6000 and 8000 m) work zones or long duration (e.g., longer than 4 h) work zones do not necessarily lead to extra crashes.

Therapeutic Plasma Exchange in Pediatric Patients With Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease After Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

OBJECTIVES: Sinusoidal obstruction syndrome/venoocclusive disease is a significant complication of hematopoietic stem cell transplantation. Due to high mortality rates, new treatment strategies have been investigated. Here, we have presented outcomes of therapeutic plasma exchange performed on patients with sinusoidal obstruction syndrome/veno-occlusive disease. MATERIAL AND METHODS: Our study included 70 pediatric patients diagnosed with sinusoidal obstruction syndrome/veno-occlusive disease. Therapeutic plasma exchange procedures in patients were evaluated retrospectively. RESULTS: There were 9 mild (12.9%), 9 moderate (12.9%), 21 severe (30%), and 31 very severe (44.2%) cases of sinusoidal obstruction syndrome/venoocclusive disease. Therapeutic plasma exchange was performed in 31 of the 70 study patients (59.6%). Moreover, 10/21 patients with severe (47.6%) and 21/31 patients with very severe (67.7%) disease underwent plasma exchange. Mean time from diagnosis of sinusoidal obstruction syndrome/venoocclusive disease to therapeutic plasma exchange initiation was 2.3 days. The 31 patients who received therapeutic plasma exchange had a total of 146 sessions. Overall survival rates at 100 days were 87.1% and 92.3% for patients who did and did not undergo therapeutic plasma exchange, respectively. When patients with mild and moderate disease who were not expected to undergo plasma exchange were excluded (n = 52), 100-day overall survival rates were 87.1% and 90.5% for those who did and did not undergo plasma exchange, respectively. When we compared severe versus very severe groups, no significant difference was found. CONCLUSIONS: Plasmapheresis had no positive effect on survival. However, overall survival in all groups was higher than that in the literature, despite the high number of patients with severe and very severe disease. Interpretation of the results is limited by the retrospective nature of the study. Thus, prospective, randomized controlled trials with larger numbers of patients are necessary to investigate the role of therapeutic plasma exchange in patients with sinusoidal obstruction syndrome/veno-occlusive disease.

Safety and Efficacy of Co-transplantation of Hematopoietic Stem Cells Combined With Human Umbilical Cord-Derived Mesenchymal Stem Cells in Children With Severe Aplastic Anemia: A Single-Center Experience.

OBJECTIVES: The mostimportant problems thatlimitthe effectiveness of allogeneic hematopoietic stem cell transplantation in patients with severe aplastic anemia are graft failure and graft-versus-host disease. Mesenchymal stem cells can support normal hematopoiesis and prevent graft-versus-host disease. We aimed to analyze the effects of combined transplant of human umbilical cord-derived mesenchymal stem cells and matched donor allogeneic hematopoietic stem cells in children with severe aplastic anemia. MATERIALS AND METHODS: We retrospectively examined 15 pediatric patients with severe aplastic anemia who received fludarabine-based reduced intensity conditioning regimen and intravenously infused human umbilical cord-derived mesenchymal stem cells at a dose of 1 × 106/kg recipient body weight within 12 to 18 hours before hematopoietic stem cells infusion. We evaluated the engraftment rate, the frequency and severity of graft-versus-host disease, and the overall survival rate. RESULTS: No patients had adverse events related to intravenously human umbilical cord-derived mesenchymal stem cells infusion. All patients achieved successful engraftment and sustained donor chimerism. The median time for neutrophil and platelet engraftment was 14 and 25 days,respectively. The frequency was 20% for grade III/IV acute graftversus- host disease and 15.3% for chronic graftversus-host disease. Patients were followed-up for a median of 33 months (range, 2-89 months). The 5-year overall survival rate was 80%. CONCLUSIONS: Combined transplant of matched donor hematopoietic stem cells with human umbilical cord-derived mesenchymal stem cells is safe in pediatric patients with severe aplastic anemia. The achievement of engraftment in all of our patients and the acceptable frequency of acute and chronic graft-versus-host disease and survival rate are encouraging.

Thalassemia-free and graft-versus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.

Fertility in Patients with Thalassemia and Outcome of Pregnancies: A Turkish Experience

Objective: In recent years, the rates of marriage and pregnancy are increasing in patients with thalassemia major. The aim of the present study was to investigate the fertility rate of thalassemic patients and the course of pregnancies in terms of mother and infant health. Materials and Methods: In this observational study patients with major hemoglobinopathy were evaluated regarding marital status, the need for assisted reproductive techniques, fertility rate, iron status, and pregnancy complications. Results: Seventeen female patients gave birth to 21 healthy infants. About one-third of the patients needed assisted reproductive techniques. Thalassemia major patients showed increased serum ferritin levels from 1203±1206 µg/L at baseline to 1880±1174 µg/L at the end of pregnancy. All babies are still alive and healthy. Conclusion: Pregnancy in patients with thalassemia can be safe for the mother and newborn with close monitoring and a multidisciplinary approach.

Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report. / Síndrome de Stevens-Johnson asociado al tratamiento con metotrexato de la leucemia linfoblástica aguda: a propósito de un caso.

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of Stevens- Johnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again.

La necrólisis epidérmica tóxica y el síndrome de Stevens- Johnson son enfermedades mucocutáneas raras que están asociadas a una evolución prolongada y a un desenlace potencialmente mortal. Principalmente están inducidas por fármacos y las tasas de mortalidad son muy elevadas. Aunque la piel es la más comprometida, también pueden estar afectados múltiples aparatos o sistemas como el cardiovascular, pulmonar, gastrointestinal y urinario. En este artículo, describimos el caso de un paciente con síndrome de Stevens-Johnson asociado al tratamiento con metotrexato, quien desarrolló insuficiencia cardíaca aguda y hemorragia gastrointestinal además de las manifestaciones en la piel. El paciente recibió un tratamiento satisfactorio con metilprednisolona e inmunoglobulina por vía intravenosa y continuó la quimioterapia con metotrexato.

Síndrome de Stevens-Johnson asociado al tratamiento con metotrexato de la leucemia linfoblástica aguda: a propósito de un caso / Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report

La necrólisis epidérmica tóxica y el síndrome de StevensJohnson son enfermedades mucocutáneas raras que están asociadas a una evolución prolongada y a un desenlace potencialmente mortal. Principalmente están inducidas por fármacos y las tasas de mortalidad son muy elevadas. Aunque la piel es la más comprometida, también pueden estar afectados múltiples aparatos o sistemas como el cardiovascular, pulmonar, gastrointestinal y urinario. En este artículo, describimos el caso de un paciente con síndrome de Stevens-Johnson asociado al tratamiento con metotrexato, quien desarrolló insuficiencia cardíaca aguda y hemorragia gastrointestinal además de las manifestaciones en la piel. El paciente recibió un tratamiento satisfactorio con metilprednisolona e inmunoglobulina por vía intravenosa y continuó la quimioterapia con metotrexato.

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of StevensJohnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again.