No significant risk of hematological malignancy in patients with neurofibromatosis type 1: single center study of children and adults

Background/AimNeurofibromatosis type 1 (NF1) is characterized by the occurrence of multisystem tumors. The objective of this study was to analyze the demographic and oncological profile of 830 NF1-individuals regarding prevalence, type, and spectrum of malignancy. Patients and methodsThe medical records of patients diagnosed with NF1 with a median age of 22.1 years (range: 0.8–81.6 years) who were followed up for malignancies from 1999 to 2018 were retrospectively reviewed. ResultsThe prevalence of malignancy occurring in patients diagnosed with NF1 was 34.8% (289/830). The most common types of neoplasia encompassed tumors strictly associated with NF1, including plexiform neurofibromas (PNF; 200/830; 24.1%) and optic pathway gliomas (91/830; 11%). The prevalence of PNFs-transforming to malignant peripheral nerve sheath tumors (MPNST) was 3.5% (7/200). The prevalence of other tumors was 4.8% (40/830). One patient was diagnosed with acute myeloid leukemia (AML), thus the risk of hematological malignancies among all patients with NF1 was 0.1% (1/830). In the population of patients with malignancies, 43/289 (14.9%) individuals were diagnosed with more than one malignancy. ConclusionsThe odds ratio (OR) of malignancy in a studied cohort of patients with NF1 was 23 ( < 0.001), while the OR of hematological malignancy was 5.1 ( = 0.1) in comparison with the general population

High risk of invasive fungal disease in children undergoing hematopoietic cell transplantation or complex anticancer therapy: the adverse role of post-transplant CMV replication

Introduction: We analyzed the epidemiology and outcomes of treatment of invasive fungal disease (IFD) in children during anticancer therapy (PHO, pediatric hematology and oncology) or after hematopoietic cell transplantation (HCT) over a period of eight consecutive years in a single-center study. Material and methods: Overall, a total of 254 HCTs were performed, and 415 children were newly diagnosed for malignancy. Incidence, epidemiology and outcome of IFD were analyzed. Results: The cumulative incidence of any IFD was 32.6% in allo-HCT, 22.2% in PHO, and 6.0% in auto-HCT patients. The incidence of proven +probable IFD was 12.6%, 10.4%, and 6.0%, respectively. As many as 77.0% HCT and 67.4% PHO of fungal episodes occurred in acute leukemia patients: the highest incidence of any IFD was observed for acute lymphoblastic leukemia (29.3% in HCT; 40.5% in PHO) and for acute myeloblastic leukemia (51.1% in HCT; 65.0% in PHO) patients. There were no significant differences in the incidence of fungal infections in both allo-HCT and PHO patients between the 2-year periods. Factors contributing to an increased risk of IFD in allo-HCT patients were: CMV replication, and acute and chronic graft-versus-host disease (GvHD). Survival from IFD was 91.9% in PHO, and 78.1% in HCT patients. Fungal pneumonia in HCT patients resolved in 62.9%, while in PHO patients it resolved in 93.5%. Conclusions: The risk of IFD in allo-HCT patients is much higher than in auto-HSCT and PHO patients. The outcome of IFD is better in PHO and auto-HCT than in allo-HCT settings

Acute non-hematological toxicity of intensive chemotherapy of acute lymphoblastic leukemia in children

IntroductionLeukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols. Patients and methodsA total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria. ResultsThe most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity. ConclusionsIntensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team

Relapsed childhood acute myeloid leukemia: prognostic factors and outcomes: experience from a single oncology center

Introduction: Over recent decades, significant progress in the treatment of childhood acute myeloid leukemia (AML) has been made. However, the relapsed disease remains a challenge. The aim of this study was to analyze therapy results in pediatric patients treated for relapsed AML in a single oncology center, with a particular focus on prognostic factors. Materials and methods: Data from patients younger than 19 years with AML diagnosed between January 1994 and December 2020 treated in the Department of Pediatric Hematology and Oncology in Bydgoszcz, Poland was analyzed, with detailed analysis of patients with relapsed disease. Results: A total of 77 children were diagnosed with AML in the analyzed period and 21 had a relapsed disease (27.3%). Bone marrow relapse was the most common. The risk factors of relapse included white blood cells &gt;100 G/L at initial diagnosis and classification to the high risk group. Late relapse was related to poorer outcomes. The 5-year probability of overall survival for the entire group was 28.6%, and this was significantly higher in patients who achieved second remission compared to those who did not (44.9% vs. 0.0%, p &lt;0.001). The main reason for death was progression of disease, which occurred in 10 patients. Conclusions: Outcomes in relapsed AML in children are still dismal. Lack of second remission suggests the need for experimental therapy

Changing risk factors in childhood acute lymphoblastic leukemia: experience from Kujawsko-Pomorski region 1976–2018

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Risk factors in childhood ALL have changed during recent decades, mostly due to treatment personalization. The aim of this study was to analyze therapy results and prognostic factors in childhood ALL in the Kujawsko-Pomorski region of Poland between 1976 and 2018. Material and methods: Data from 495 patients (0–18 years old) diagnosed with ALL from the Kujawsko-Pomorski region between 1976 and 2018 was analyzed. Prognostic factors were analyzed separately in specific therapeutic groups, which were defined by several therapy protocols. Results: Prognostic factors have changed over the course of consecutive therapeutic periods. Between 1976 and 1988 (the first and second therapeutic protocols), central nervous system involvement was the most important risk factor. During the third therapeutic period, an unsatisfactory treatment response on days 8 and 14 was related to a poor outcome. In 1995–2002, the risk factors were hepatomegaly, splenomegaly, lymph nodes involvement, and unsatisfactory therapy response on days 15 and 33. Between 2002 and 2011, immunophenotype other than ‘common’ and hemoglobin level at diagnosis were the risk factors, and a lack of BCR-ABL aberration was related to better therapy results. During the final analyzed period (2011–2018), failure to achieve remission on day 33 was a risk factor, and patients classified as non-high risk group and those aged &lt;6 years had better outcomes. Conclusions: The changing profile of risk factors in ALL has reflected progress in ALL therapy, with the gradual elimination of factors related to poor outcomes, mostly due to modifications in treatment and the development of diagnostic methods as well as therapy monitoring

Management of early period of hematopoietic cell transplantation in ambulatory/outpatient setting with primary antimicrobial prophylaxis: an attractive option

The concept of ambulatory/outpatient transplantations is based on variable distribution and location of performing basic stages of hematopoietic cell transplantation (HCT): central venous catheter insertion, high-dose chemotherapy administration, hematopoietic stem cells infusion, and supportive care during aplastic phase. Our objective was to present the concept of outpatient transplantation and to review the available data on prophylaxis of infectious complications early after outpatient transplantation. In our general recommendations, patients, family members and caregivers should be trained before discharge on the careful monitoring of fever and other signs and symptoms of infections. The clinical evaluation of patients should be performed twice weekly until clinical recovery. Standard transplant approach should be applied for dose of CD34+ cells, use of granulocyte colony-stimulating factor after HSC infusion, use of primary antimicrobial prophylaxis, and supportive care. Antimicrobial prophylaxis for ambulatory auto-HCT patients should be the same as for a conventional inpatient setting, including antibacterial, antiviral and anti-Pneumocystis jiroveci pneumonia (PjP) prophylaxis. For patients undergoing allo-HCT in an outpatient setting, the general recommendations are the same as for auto-HCT patients. Frequent monitoring of immunosuppressive treatment is recommended. Monitoring for cytomegalovirus infection and Aspergillus galactomannan should be the same as for conventional allo-HCT. Primary anti-mold prophylaxis is strongly suggested. Ambulatory auto-HCT is feasible and safe, making this an important alternative option. This is an especially attractive option for multiple myeloma patients, as it has a very low transplant-related mortality risk. Obviously, ambulatory auto-HCT cannot be regarded as a routine procedure

Autoimmune cytopenias complicating hematopoietic cell transplantation

Immune cytopenias after allogeneic hematopoietic cell transplantation are rare, albeit increasingly recognized, complications. Autoimmune diseases are serious complications of HCT and include immune-mediated cytopenias i.e. autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia. Severe cytopenia is usually defined by decreases of hemoglobin concentration below 7 g/dL, of platelet count below 20 G/L, or of absolute granulocyte count below 0.5 G/L, and it is mediated by the presence of auto-antibodies. ITP occurring in combination with AIHA is known as Evans syndrome. Immune dysregulation is caused by impaired immune reconstitution and/or loss of self-tolerance. Primary risk factors of autoimmune cytopenias include: peripheral blood or cord blood as a stem cell source, unrelated HCT, non-malignant disease, use of alemtuzumab, acute/chronic graft-versus-host disease (GvHD), cytomegalovirus reactivation, infections, and, in pediatric settings, conditioning omitting total body irradiation. Diagnosis of autoimmune cytopenia is challenging due to a broad differential diagnosis: primary or secondary graft failure, infections, GvHD, disease relapse, drug-induced side effects, transplant-associated thrombotic microangiopathy, ABO-incompatibility, or disseminated intravascular coagulation. Treatment should be tailored to the individual patient, and ranges from watchful waiting to aggressive management in life-threatening situations. Apart from specific treatment adjusted for specific cytopenia, supportive care should include transfusions of leukocyte-reduced and irradiated red blood cell concentrates or pathogen-reduced platelet concentrates; treatment of infections and GvHD; modification of immunosuppression; and supplementation with microelements. Autoimmune cytopenias are usually highly resistant to standard therapy and are associated with increased risks of high morbidity and mortality, particularly when coexisting with other post-transplant complications

Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report

Abstract Background Pediatric autoinflammatory diseases are rare and still poorly understood conditions resulting from defective genetic control of innate immune system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2 protein, taking part in maintenance of immune homeostasis. Clinical form of resultant autoinflammatory condition depends on NOD2 genotype; usually patients with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory disease (NAID) or Crohn’s disease. Case presentation We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. Overlapping manifestations of two syndromes raised a significant diagnostic challenge, until next-generation molecular test (NGS) identified presence of three pathogenic variants of NOD2 gene: P268S, IVS8+158, 1007 fs, and established the ultimate diagnosis. Conclusion Presence of multiple genetical abnormalities resulted in an ambiguous clinical presentation with overlapping symptoms of Blau syndrome and NAID. Final diagnosis of autoinflammatory disease opened new therapeutic possibilities, including the use of biological treatments