thioguanine-anhydrous and Leukemic-Infiltration

We present the case of an 11.5-year-old girl with M1 acute myelogenous leukemia (AML) who had isolated extramedullary relapse develop in both breasts 12 months after diagnosis and 7 months off chemotherapy. She received further chemotherapy, focal radiation therapy, then underwent a matched, unrelated bone marrow transplant and continues in remission 37 months later. Review of the literature revealed 10 cases in other children younger than 21-years-old with AML and breast involvement. These cases are summarized, and potential pathophysiologic mechanisms of spread are discussed. Breast involvement in AML is rare in children. However, regular breast examinations should be performed as part of routine follow-up in all girls with AML.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow Transplantation; Breast; Child; Combined Modality Therapy; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Graft vs Host Disease; Humans; Idarubicin; Immunologic Factors; Interleukin-2; Leukemia, Myeloid, Acute; Leukemic Infiltration; Radiotherapy, High-Energy; Recurrence; Salvage Therapy; Thioguanine; Transplantation Conditioning; Vidarabine

To evaluate whether children with acute myeloblastic leukemia (AML) presenting with extramedullary infiltration (EMI) have different clinical, morphologic features and prognosis from children without EMI, a 127 consecutive previously untreated children with AML were entered in this study. Fifty-one children (40%) had EMI at diagnosis and 27% of these showed multiple site involvement. Twenty-seven of 127 children (21%) presented myeloid tumors. No age related differences in the incidence of EMI was noted. However, analysis of clinical and biological features at diagnosis showed that WBC count > or =50 x 10(9) l(-1), hepatosplenomegaly >5 cm, FAB AML-M4 and AML-M5 subtypes and CD13, CD14 expression of bone marrow (BM) leukemic cells (>20%) were more frequent in children with EMI. Two consecutive treatment protocols were used. In both protocols remission was achieved with combined high-dose methylprednisolone (HDMP) as a differentiating and apoptosis inducing agent with mild cytotoxic chemotherapy (low-dose cytosine arabinoside (LD Ara-C), weekly mitoxantrone and Ara-C or 6-thioguanine). Administration of short-course (4-7 days) HDMP (20-30 mg/kg per day) alone resulted in a remarkable decrease in peripheral blood, BM blasts and in the size of EMI in responding patients. In both protocols, remission rate in patients with EMI was 71 and 80%, which was lower than that of the patients without EMI (87 and 89%). This may be attributed to the higher frequency of unfavorable features in children with EMI. However, in patients who presented with myeloblastoma and treated with a more intensive post-remission therapy (AML-94), the 4-year disease-free survival (DFS) and event-free survival (EFS) rates were not found to be significantly different from children who had no EMI (P>0.05). Whereas, the outcome of children who presented with gingival infiltration did not improve. In further studies, the prognostic significance of different localisation of EMI and the effect of addition of HDMP to cytotoxic chemotherapy should be explored in larger series.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Bone Marrow Cells; CD13 Antigens; Child; Child, Preschool; Cytarabine; Female; Humans; Leukemia, Myeloid; Leukemic Infiltration; Lipopolysaccharide Receptors; Male; Methylprednisolone; Mitoxantrone; Prognosis; Remission Induction; Survival Rate; Thioguanine; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Colitis; Colon; Cytarabine; Daunorubicin; Dexamethasone; Etoposide; Female; Gastrointestinal Hemorrhage; Humans; Immunohistochemistry; Infant; Leukemia, Myeloid, Acute; Leukemic Infiltration; Leukocyte Common Antigens; Peroxidase; Sigmoidoscopy; Thioguanine

During T cell selection in the thymic cortex more than 90% of the thymocytes are eliminated by apoptosis. Based on this biology, we propose to define blasts of T cell acute lymphoblastic leukemia (ALL) with the phenotype of cortical thymocytes (CD1+ and/or CD4+ 8+) as selection-related (SR) and all other T-ALL immunophenotypes as non-selection-related (NSR). The COALL cooperative treatment studies for childhood ALL offer a tool to study the outcome in T-ALL subgroups as children with T-ALL are allocated uniformly to the high risk arm of the protocol. In the COALL-85, -89 and -92 protocols, 39/83 cases presented as SR and 44/83 cases as NSR. Five-year event-free survival of SR phenotype is significantly better compared to the NSR group (0.87 +/- 0.06 vs 0.66 +/- 0.07, log rank test, P = 0.01). T-ALL with SR phenotype is a distinct subgroup of leukemia with excellent prognosis under a high risk treatment protocol.

Topics: Adolescent; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System; Child; Child, Preschool; Clonal Deletion; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Germany; Humans; Immunophenotyping; Infant; Leukemia-Lymphoma, Adult T-Cell; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Multicenter Studies as Topic; Neoplastic Stem Cells; Prednisolone; Remission Induction; Risk; T-Lymphocyte Subsets; Teniposide; Thioguanine; Treatment Outcome; Vincristine

Extramedullary masses as features of acute monoblastic leukemia are rare. Acute monoblastic leukemia is an uncommon type of nonlymphocytic leukemia that generally first manifest with signs and of bone marrow failure, articular and/or neurological symptoms. This study describes one patient with acute monoblastic leukemia in whom the initial manifestation of the disorder was related to testicular mass.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Cytarabine; Doxorubicin; Humans; Leukemia, Monocytic, Acute; Leukemic Infiltration; Male; Testis; Thioguanine