The outcome of relapsed childhood acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantations: A single-center experience.

In children with high-risk childhood acute leukemia who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT), relapse is still the leading cause of treatment failure. The prognosis is poor, yet prospective studies have only limited data on risk factors and outcomes. We aimed to understand the outcomes and prognostic factors for patients with acute lymphoblastic leukemia (ALL) who relapsed following allo-HSCT. We analyzed retrospectively 46 children with childhood acute lymphoblastic leukemia who had relapsed after receiving their first alloHSCT. All these patients received salvage chemotherapy which consisted of fludarabine, cytarabine, and idarubicin before performing a second alloHSCT. The median follow-up of the 46 patients after the first transplantation was 366 days. The median time from first allo-HSCT to relapse was 278.4 ± 238.4 days. Forty-six patients received salvage chemotherapy before the second alloHSCT, and CR was achieved in 32 of 46 patients. However, only 17 (37%) of 46 patients received a second allo-HSCT, and 15 of 46 patients died from disease progression, infections, and bleeding. Twelve patients are still alive after the second allo-HSCT. Two-year overall survival (OS) was 38.9%. Local therapy was given to 10 (21.8%) patients, either as part of systemic therapy or alone. In multivariate analyses, the time of relapse and curative salvage therapy with a second allo-HSCT were identified as significant prognostic factors for OS. Children with leukemia who had relapsed after the first allo-HSCT received salvage chemotherapy. Our statistical analysis showed that the second HSCT could be beneficial for outcomes if patients relapsed beyond 180 days of the first allo-HSCT.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

The Efficacy of Three Different Oral Hygiene Regimens in Preventing Chemotherapy-Induced Oral Mucositis in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

BACKGROUND: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies. METHODS: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients. RESULTS: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation. CONCLUSION: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis.

Pneumatosis cystoides intestinalis mimicking free intraabdominal air following chemotherapy for relapsed acute myeloblastic leukemia in a transplanted neutropenic child: a case report.

BACKGROUND: Pneumatosis cystoides intestinalis (PI) is a rare but important condition in which widespread air sacs are found in the submucosa, and subserosa of the bowel wall. Although it has several etiologies, children receiving chemotherapy are at risk for PI. Preferred imaging tools for the diagnosis are abdominal direct radiography and computed tomography. In patients with PI, rupture of intramural air sacs is the source of benign pneumoperitoneum, causing free air without true intestinal perforation. Intestinal perforation or obstruction are indications for surgical intervention. CASE: Here, we present a 4-year-old patient diagnosed with acute myeloblastic leukemia (AML), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) and developed PI after HSCT. The patient was consulted to the pediatric surgery department, and her oral feeding was stopped. Broad spectrum antibiotics (teicoplanin, metronidazol and vancomycin) were initiated. Her fever increased during the 24-hour monitoring, there was no stool passage, CRP ( > 25 mg/dL, normal value < 1 mg/dL) and abdominal distension increased and there was prolonged neutropenia and radiologic investigations could not rule out intestinal perforation, so the patient underwent exploratory laparotomy. No intestinal perforation was found. There was no sign in the intestinal wall and numerous gas-filled cysts of various sizes. CONCLUSIONS: PI is an uncommon complication, and direct radiography/computed tomography scans are very helpful in making the diagnosis in suspicious cases. PI, should be kept in mind, especially in transplanted or relapsed leukemia patients receiving intensive chemotherapy.

Busulfan-Based and Treosulfan-Based Myeloablative Conditioning for Allogeneic Transplantation in Children with Thalassemia Major: a Single-Center Experience From Southern Turkey.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant is the only curative treatment for patients with transfusion-dependent thalassemia major. In recent years, a number of novel approaches have improved patient outcomes and quality of life by minimizing the toxicity of conditioning regimens. The objective of this study was to compare the role of treosulfan- and busulfan-based conditioning in transfusion-dependent thalassemia. MATERIALS AND METHODS: Data were collected retrospectively on 121 children with beta thalassemia major who underwent hematopoietic stem cell transplant using treosulfan-based (n = 37) or busulfan-based (n = 84) conditioning regimens between 2012 and 2022. RESULTS: Two-year overall survival was 87.5% in the busulfan-based conditioning group and 91.1% in the treosulfan-based conditioning group.The group given the busulfan regimen compared with treosulfan regimen had significantly increased number of side effects (58.3% vs 21.6%, respectively; P < .001). When the busulfan-based regimen by level was evaluated, we observed no significant differences between the frequency of side effects according to drug serum levels. In addition, no significant differences were shown between the 2 regimen groups for cumulative incidence of acute and chronic graft-versus-host disease. CONCLUSIONS: The safety and effectiveness of a treosulfan-based myeloablative conditioning regimen has been confirmed by ourretrospective investigation of pediatric patients with beta thalassemia.

Hemophagocytic lymphohistiocytosis in children with Griscelli syndrome type 2: genetics, laboratory findings and treatment.

Griscelli syndrome is a rare inherited autosomal recessive syndrome that causes immunodeficiency. Hemophagocytic lymphohistiocytosis (HLH), which is characterized by a high mortality rate, may develop because of Griscelli syndrome type 2 (GS2). We aimed to share our experience with the diagnosis and treatment methods of patients who developed HLH secondary to GS2. Patients with GS2 who were diagnosed and treated for HLH between 2017 and 2022 at the Cukurova University Division of Pediatric Allergy & Immunology and Division of Pediatric Hematology were included in the study. Microscopic examination of the hair shaft and next-generation sequencing for molecular genetic testing of RAB27A helped in the diagnosis of GS2. The first clinical presentation of 8 patients was HLH. One patient presented with CNS involvement and two patients presented with recurrent fever. Over 5 years, GS2 was diagnosed in 15 patients, of whom 11 (73.3%) developed HLH. The HLH-2004 protocol was used to treat these patients. Hematopoietic stem cell transplantation (HSCT) was performed in five patients who were matched with suitable donors. While all patients who underwent HSCT were alive, three patients who could not undergo HSCT because no donor could be found died. Deletion of CAAGC at nucleotides 514_518 in GS2 patients is associated with CNS involvement and a poor prognosis. HLH may be the first sign of presentation in patients with GS2. Although further research is needed, regardless of the conditioning regimen utilized, early HSCT remains the primary therapy option for preventing GS2-induced mortality in HLH.

The prevalence and outcomes of thrombocytopenia in a neonatal intensive care unit: a three-year report.

Neonatal thrombocytopenia is one of the most common hematologic disorders in neonatal intensive care units (NICUs). The purpose of this study was to determine the prevalence of thrombocytopenia and whether thrombocytopenia has an effect on the occurrence of intraventricular hemorrhage (IVH) ≥ grade 2 and on mortality rate. This study was carried out retrospectively in neonates admitted to NICU of Cumhuriyet University in Sivas, Turkey, between 2009 and 2012. Among 2218 neonates evaluated, 208 (9.4%) developed thrombocytopenia. The prevalence of IVH ≥ grade 2 was more in infants with thrombocytopenia (7.2%) than in those without thrombocytopenia (4.4%), although this was not statistically significant (P = .08). In univariate analysis, IVH ≥ grade 2 was higher in cases with very severe thrombocytopenia (35.7%, n = 5) than in those with mild (2.1%, n = 2), moderate (4.7%, n = 3), and severe thrombocytopenia (15.2%, n = 5) (P = .04). Multivariate logistic regression analysis showed that birth weight <1500 g (OR 6.2, 95% CI 3.4-9.8; P = .0001), gram-negative sepsis (OR 2.5, 95% CI 1.8-4.2; P = .01), very severe thrombocytopenia (OR 1.3, 95% CI 1.1-2.1; P = .03), and platelet transfusion ≥2 (OR 7.3, 95% CI 4.1-12.1; P = .001) were significant risk factors for mortality. The results of our study suggest that outcomes of neonates with thrombocytopenia depend not only on platelet count but also on decreased gestational age or birth weight, prenatal factors, and sepsis.

Splenic rupture presenting with marked scrotal ecchymosis in a 2-day-old newborn.

Splenic rupture is a rare and severe condition in neonates. The signs and symptoms are vague and non-specific and are often not recognised before the onset of hypovolaemic shock or death. A 2-day-old infant presented with scrotal ecchymosis, and ultrasonography detected haemorrhage in the scrotal, right inguinal and adrenal regions. Computed tomography demonstrated a peri-splenic haematoma. Haemoglobin (Hb) was 2.79 g/dL and, despite repeated transfusions, the Hb level could not be sustained. Exploratory laparotomy detected a large haematoma in the splenic region, and, because of the uncontrolled haemorrhage, splenectomy was required.

PHACE Syndrome in a Child with Structural Malformations of the Brain.

PHACE syndrome is an acronym that describes a neurocutaneous condition, consisting of posterior fossa malformations that coexist with large facial hemangiomas, eye anomalies, and cardiac/aortic defects. The prognosis of the disease has not been clearly identified. There appears to be a risk of stroke in children with arterial anomalies. Radiological examinations play a considerable role in determining the degree of intracranial, cardiac involvement and the probable complications. In this article, we reported a 4-month-old boy with PHACE syndrome that has been diagnosed through a large segmental infantile hemangioma involving the eye and over the left half of the face in brain magnetic resonance imaging and magnetic resonance angiography findings. One month after starting propranolol therapy, there was a noticeable reduction in the size of the lesions. Almost complete resolution of the hemangioma was seen after a 6 months of propranolol therapy.

Risk Assessment for BK Virus-Associated Hemorrhagic Cystitis After Pediatric Hematopoietic Stem Cell Transplant: A Single-Center Retrospective Cross-Sectional Study.

OBJECTIVES: BK virus-associated hemorrhagic cystitis is a common complication of allogeneic hematopoietic stem cell transplant. It is known to be associated with cyclophosphamide therapy and the intensity of the conditioning regimen as well as infection with the BK virus. Data are limited for BK virus-associated hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Therefore, we aimed to identify the risk factors and etiology of BK virus-associated hemorrhagic cystitis and determine the factors that may improve the treatment efficacy. MATERIALS AND METHODS: Data from recipients of allogeneic hematopoietic stem cell transplant were retrospectively analyzed. These data included information about age, sex, underlying disease, the details of ablative conditioning, graft-versus-host disease prophylaxis, donor type, stem cell source, history of acute graft-versus-host disease, and cytomegalovirus reactivation. RESULTS: A total of 50 patients developed BK virusassociated hemorrhagic cystitis among 334 patients. Symptoms associated with BK virus-associated hemorrhagic cystitis manifested an average of 45.3 days after transplant. Most of the patients had grade 2 and grade 3 hemorrhagic cystitis. Risk factor analysis revealed that haploidentical donor type, treatment with busulfan and cyclophosphamide as part of conditioning regimen, and history of total body irradiation increased the risk of BK virus-associated hemorrhagic cystitis in the pediatric recipient population. CONCLUSIONS: We found that, despite current conditioning regimens, BK virus-associated infection still leads to a considerable incidence rate of hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Patients with a haploidentical donor and a history of busulfan and cyclophosphamide treatment or total body irradiation had a higher risk of BK virus-associated hemorrhagic cystitis. Thus, we suggest that patients with these factors should be followed closely after allogeneic hematopoietic stem cell transplant.