thioguanine-anhydrous and Stomatitis

Approximately 25% of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse, with bone marrow being the most common site of recurrence. The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL.. Thirty pediatric patients with relapsed medullary (n = 18) and extra-medullary (n = 12) ALL were enrolled at three pediatric institutions. Following receipt of induction and the first Block A and Block B of intensification, each patient was evaluated for toxicity, efficacy in achieving remission, and long-term survival. Additionally, minimal residual disease (MRD) detection by multidimensional flow cytometry (MDF) was performed.. During induction, the major non-hematopoeitic toxicities were mucositis (30% of patients) and bacteremia (50% of patients). Two patients (7%) died of toxicity during induction. Toxicity during intensification Block 1A and 1B was markedly reduced. Eight-nine percent of patients with marrow disease achieved a remission following induction and intensification. The event-free survival (EFS) for all patients at 2 and 4 years were 60% (95% CI: 42-78%) and 49% (95% CI: 30-68%), respectively.. This regimen for patients with relapsed ALL was successful in achieving a second remission for the majority of patients with acceptable toxicity.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bacteremia; Bone Marrow Neoplasms; Child; Child, Preschool; Cytarabine; Dexamethasone; Etoposide; Female; Flow Cytometry; Humans; Idarubicin; Ifosfamide; Infant; Infusions, Intravenous; Leucovorin; Male; Mesna; Methotrexate; Mouth Mucosa; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Stomatitis; Thioguanine; Treatment Outcome; Vincristine

The efficiency and toxicity of treatment regimens for nonintensive cytoreduction in 57 outpatients with refractory acute leukemia (mean age 56 years, 51 AML, six ALL/AUL) were retrospectively studied. Seventeen patients received one treatment regimen, 19 patients two treatment regimens, and 21 patients three or more treatment regimens. The treatment regimens analyzed were 6-thioguanine p.o. (daily) (T), 6-thioguanine p.o. (4-7 days/week) + cytarabine s.c./i.v. (once a week) (T+C), 6-mercaptopurine p.o. (daily) (MP), 6-mercaptopurine p.o. (daily) + methotrexate p.o./i.v. (once a week) (MP+MTX), etoposide p.o. (daily) (E), and mitoxantrone i.v. (M). The median leukocyte count was higher for M (73 x 10(9)/l) than for the other treatment regimens (T: 27 x 10(9)/l, T+ C: 37 x 10(9)/l, MP: 24 x 10(9)/l, MP + MTX: 30 x 10(9)/l, E: 31 x 10(9)/l). A cytoreduction >50% in the peripheral blood was achieved by T in 11/19, by T+C in 7/11, by MP in 5/8, by MP+MTX in 3/6, by E in 3/4, and by M in 16/22 patients. The period of cytoreduction was regarded as the duration of response - T: median 53 days, range 5-98; T+C: median 61 days, range 14-226; MP: median 37 days, range 4-192; MP + MTX: median 58 days, range 36-59; E: median 121 days, range 26-159; M: median 39 days, range 8-78. T and T + C were well tolerated by all but three patients (stomatitis, diarrhea, WHO grade 2). MP was accompanied by a rise of transaminases (WHO 1-3) in 5/6 patients. E led to stomatitis (WHO 1,2) in 4/5 and M to nausea/vomiting (WHO 1,2) in 5/22 and to stomatitis (WHO 2) in 4/22 cases. The mean survival time after start of palliative cytoreduction was 16 weeks (2-65). In summary, 6-thioguanine +/- cytarabine was best tolerated with effective but in oral monotherapy - often protracted cytoreduction in 60% of patients. Mitoxantrone showed tolerable side effects and potent cytoreduction in 73% of patients even after ineffective palliative pretreatment. Palliative cytoreductive therapy does not reduce the quality of life and can prevent complications of significant leukocytosis in refractory acute leukemia.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Diarrhea; Female; Humans; Injections, Intravenous; Injections, Subcutaneous; Leukemia; Leukocyte Count; Male; Mercaptopurine; Methotrexate; Middle Aged; Nausea; Palliative Care; Retrospective Studies; Stomatitis; Thioguanine

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosomes, Human, 21-22 and Y; Cytarabine; Daunorubicin; Humans; Isotretinoin; Leukemia, Myeloid; Leukopenia; Liver; Middle Aged; Stomatitis; Thioguanine; Thrombocytopenia; Time Factors; Tretinoin

Topics: Adenocarcinoma; Alopecia; Antineoplastic Agents; Azaserine; Carcinoma, Squamous Cell; Diarrhea; Drug Eruptions; Drug Therapy; Geriatrics; Guanine; Leukopenia; Nausea; Neoplasms; Stomatitis; Thioguanine; Thrombocytopenia; Toxicology