mercaptopurine and Leukemia--Myelomonocytic--Juvenile

Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Mercaptopurine; Transplantation, Homologous

Juvenile myelomonocytic leukemia(JMML) is a pediatric myeloproliferative disorder. Allogeneic hematopoietic stem cell transplant (HSCT) is the only curative treatment for JMML. Pre-transplant therapy is a matter of controversy, and there are no firm recommendations. Whether chemotherapy is effective in achieving durable remission is questionable. Patients diagnosed as JMML at our center from January-2014 to December-2019 were retrospectively analyzed. All patients treated with at least one cycle of sequential therapy with subcutaneous cytarabine and oral 6-mercaptopurine were further assessed. The total number of patients diagnosed during the study period was 33. Patients were divided into two groups: patients who did not get any chemotherapy (

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Leukocyte Count; Mercaptopurine; Platelet Count; Remission Induction; Retrospective Studies; Spleen; Treatment Outcome

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder of childhood. Major progress has been achieved in diagnosis and the understanding of the pathogenesis of JMML by identifying the genetic pathologies that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL are found in approximately 80% of JMML patients. Distinct clinical features have been reported to be associated with specific gene mutations. The advent of genomic studies and recent identification of novel genetic mutations in JMML are important not only in diagnosis but also in the management and prognosis of the disease. Herein, we present 2 patients with JMML harboring different mutations, NRAS and c-CBL, respectively, with distinct clinical features and different therapeutic approaches.. Juvenil myelomonositik lösemi (JMML) çocukluk çağında nadir görülen klonal myeloproliferatif bir hastalıktır. Hastalarda genetik patolojiler saptandıkça JMML’nin tanı ve patogenezini anlamada önemli ilerlemeler kaydedilmiştir. Bu hastaların yaklaşık %80’inde RAS, NF1, PTPN11 ve CBL gen mutasyonları bulunmuştur. Belirli klinik bulgular ile spesifik gen mutasyonları arasında ilişki olduğu bildirilmektedir. JMML’de genomik çalışmalardaki gelişmeler ve son yıllarda tanımlanmış yeni genetik mutasyonların saptanması sadece hastalığın tanısı için değil, tedavi ve prognozunda da önem taşımaktadır. Burada NRAS ve c-CBL mutasyonları olan iki JMML’li hasta, belirli klinik bulguları ve farklı tedavi yaklaşımları ile sunulmaktadır.

Topics: Abnormalities, Multiple; Allografts; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Autoimmunity; Cytarabine; Exons; Female; Genes, ras; Genetic Heterogeneity; Germ-Line Mutation; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Male; Mercaptopurine; Mutation, Missense; Point Mutation; Prednisolone; Proto-Oncogene Proteins c-cbl; Remission Induction

Topics: Child, Preschool; Drug Resistance, Neoplasm; Female; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Male; Mercaptopurine; Mutation; Neoplastic Stem Cells; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Signal Transduction; Treatment Outcome

Juvenile myelomonocytic leukemia is a rare malignancy that occurs in pediatric patients. Previous reports, have described leukemic cells may infiltrate many organs, such as the lungs, skin, liver, spleen, and intestines, but not the central nervous system, although central nervous system infiltration remains a point of concern in every patient with acute leukemia. Here, we present one case of a boy with juvenile myelomonocytic leukemia who developed multiple lesions in the brain while undergoing chemotherapy with 6-mercaptopurine and cytarabine. We diagnosed the central nervous system involvement by magnetic resonance imaging, cerebrospinal fluid cytology, and the patient's clinical course. He was treated with a high dose of cytarabine and intrathecal chemotherapy, then with unrelated cord blood stem cell transplantation. He has been in a first complete remission for more than 18 months after cord blood stem cell transplantation without any neurological sequelae. In conclusion, we encountered a boy with juvenile myelomonocytic leukemia who developed central nervous system lesions under standard chemotherapy. We subsequently switched treatment to central nervous system-oriented chemotherapy, which resulted in a good clinical condition and successful cord blood stem cell transplantation.

Topics: Antimetabolites, Antineoplastic; Brain; Cytarabine; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Male; Mercaptopurine; Stem Cell Transplantation

The development of xanthogranulomas has been linked to hematologic malignancies in children and adults, based on a number of reports in the literature. In children, a specific association between juvenile xanthogranuloma, neurofibromatosis 1, and juvenile myelomonocytic leukemia has been described. We report a case of a 9-month-old child, without a known diagnosis of neurofibromatosis 1, who presented with hepatosplenomegaly, anemia, thrombocytopenia, and multiple cutaneous nodules, which were confirmed to be juvenile xanthogranulomas upon biopsy. A concurrent work-up showed that the child had juvenile myelomonocytic leukemia. Although cutaneous juvenile xanthogranulomas are benign lesions, in several reported cases they have been shown to herald leukemia. This association between xanthogranulomas and hematologic malignancy is poorly understood. Juvenile xanthogranulomas have a number of morphologic variants and clinical presentations that can be confused with the cutaneous lesions of Langerhans cell histiocytosis and dermatofibroma. Recognition of the broad clinicopathologic spectrum of juvenile xanthogranulomas is critical for proper diagnosis.

Topics: Anemia; Antimetabolites; Hepatomegaly; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Male; Mercaptopurine; Splenomegaly; Stem Cell Transplantation; Thrombocytopenia; Treatment Outcome; Xanthogranuloma, Juvenile

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder affecting young children. The natural course of JMML is rapidly fatal with 80% of patients surviving less than three years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of JMML. We report a case of a 23-month-old girl who presented with an upper respiratory tract infection, fever, rash, diarrhea, hepatosplenomegaly and abdominal distention. Severe elevation of white blood cell count with monocytosis and myeloid progenitors in the peripheral blood was also detected. Bone marrow smear showed morphology suggestive of JMML, an unspecific immune phenotype and a normal karyotype. DNA analysis revealed a mutation in the PTPN11 gene. Therefore, the final diagnosis of JMML with somatic PTPN11 mutation was established. Following three months of cytostatic therapy with 6-mercaptopurine and low doses of cytarabine partial remission was achieved and allogeneic HSCT was successfully performed. Six months after the diagnosis, the girl was in a good condition and in a complete remission of JMML. Early diagnosis and allogeneic HSCT were crucial for successful treatment outcome.

Topics: Antimetabolites, Antineoplastic; Biopsy, Fine-Needle; Cytarabine; Eosine Yellowish-(YS); Female; Humans; Infant; Leukemia, Myelomonocytic, Juvenile; Mercaptopurine; Methylene Blue; Protein Tyrosine Phosphatase, Non-Receptor Type 11