Syndrome of inappropriate secretion of antidiuretic hormone in nasopharynx carcinoma.

The syndrome of inappropriate secretion of antidiuretic hormone (ADH) or SIADH has been reported in various disorders. We report a pediatric patient with nasopharynx carcinoma who may have developed a clinical SIADH with severe hyponatremia and generalized seizure during the administration of intravenous hydration. We propose that the inappropriately high plasma level of ADH led to the inability to excrete sufficient amounts of free water during a hyperhydration protocol with a relatively hypotonic fluid, which resulted in acute hyponatremia and central nervous system involvement. To avoid this complication, intravenous hydration before chemotherapy in children with nasopharynx carcinoma should be performed at a slower infusion rate and with a sodium chloride concentration of more than half isotonic.

Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease.

PURPOSE: To evaluate in a randomized trial the impact of three versus six cycles of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) chemotherapy in favorable-prognosis and CVPP versus doxorubicin, vincristine, prednisone, and etoposide (AOPE) plus involved-field radiotherapy (RT) in intermediate-prognosis previously untreated Hodgkin's disease. PATIENTS AND METHODS: Of 256 patients evaluated, 80 with a favorable prognosis according to a prognostic index designed by the Grupo Argentina de Tratamiento de Leucemia Aguda (GATLA) were randomized to three versus six cycles of CVPP without RT and 176 with intermediate risk to CVPP versus AOPE, both for six cycles with RT between the third and fourth cycles of 30 Gy to the involved areas at diagnosis. CVPP consisted of intravenous (I.V.) cyclophosphamide and vinblastine on days 1 and 8, and oral procarbazine and prednisone on days 1 to 14, every 28 days. AOPE consisted of I.V. doxorubicin and vincristine on day 1, oral prednisone on days 1 to 5, and I.V. etoposide on days 1 and 3, every 28 days. RESULTS: Complete remission was obtained in 39 of 41 (95%) patients treated with three cycles of CVPP and 36 of 39 (92%) treated with six cycles in the favorable-risk group (difference not significant [NS]). In the intermediate-risk group, 89 of 92 (97%) treated with CVPP plus RT versus 75 of 84 (89%) treated with AOPE plus RT achieved a complete remission (P = .05). At 60 months, the event-free survival (EFS) and overall survival rates in the favorable-risk group were 80% and 91% for CVPP x 3 and 84% and 97% for CVPP x 6, respectively (P = NS). In the intermediate-risk group, 60-month EFS rate for CVPP plus RT was 85%, compared with 66% for AOPE plus RT (P = .009). The overall survival rate was 95% versus 87% respectively (P = .157). CONCLUSION: Three cycles of CVPP without RT are equally effective as six cycles in the favorable-risk group. However, in the intermediate-group, CVPP plus RT is superior to AOPE plus RT, with significantly fewer events before and after induction (P = .009), without a difference in overall survival.

Alternating pulses of vincristine-prednisone with cytarabine-cyclophosphamide versus vincristine-prednisone in the maintenance therapy of acute lymphoblastic leukemia.

From January 1976 to December 1978, 347 children less than or equal to 15 years of age were entered in a collaborative controlled trial which included: induction (vincristine-daunorubicin-prednisone); intensification (cytarabine-cyclophosphamide); CNS prevention (intrathecal methotrexate-dexamethasone, three doses during induction and three weekly doses during the first month of maintenance, followed by one dose every 3 months for 48 months); and maintenance (6-mercaptopurine daily and methotrexate twice weekly with reinforcement pulse doses of either 1.5 mg/m2 X 1 of vincristine plus 40 mg/m2/day X 7 of prednisone [Arm A] or vincristine-prednisone alternating with 50 mg/m2 of cytarabine sc every 12 hours X 10 plus 600 mg/m2 X 1 of cyclophosphamide [Arm B]). Pulses were performed in both arms at 1, 2, 3, 4, and 6 months and every 3 months thereafter. Randomization was stratified according to age and initial wbc count. A total of 89% (310/347) of patients achieved complete remission. Duration of continuous complete remission was evaluated according to prognostic factor groups. At 5 years, 34.5% of patients with good prognosis, 24.8% with intermediate prognosis, and 12.8% with poor prognosis are in continuous complete remission. There is statistical difference between good versus poor prognosis (P less than 0.0005) and intermediate versus poor prognosis (P less than 0.025). Moreover, 5-year survival is 50.9%, 35.2%, and 18.2% in the good-, intermediate-, and poor-prognosis groups, respectively. Duration of continuous complete remission up to the first event (ie, bone marrow, CNS, or other extramedullary relapse, or death in complete remission), according to prognostic groups, did not differ in relation to reinforcement pulses (Arm A or B). We conclude that there was no benefit in alternating pulses of vincristine-prednisone with cyclophosphamide-cytarabine as used in this study.

Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity started to be recognized as CT scan abnormalities and neuropsychologic alterations, mainly in children. Two questions were analyzed in the present report: (1) Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse in patients treated early in remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t. MTX-DMT given during induction and maintenance equally as effective as cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to answer the first question. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of 135 patients) and was 11% (17 of 150) in the untreated group. In patients with a WBC count greater than 50,000, it was 16% (6/37) in the treated group and 19% (6/31) in the control group. No difference was observed according to treatment in both prognostic groups. Patients in this study were retrospectively compared with a consecutive protocol in which patients received 3 doses of i.t. MTX-DMT alone during induction plus 3 doses weekly during the first month of remission and every 3 mo thereafter. The incidence of primary CNS leukemia at 60 mo in patients with a WBC count less than 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. This difference was not significant. However, the relapse-free survival at 60 mo was 26% and 41%, respectively, (p less than 0.0005). The incidence of primary CNS relapse in patients with a WBC count more than 50,000 at 48 mo was 28% in the irradiated group and 42% in the nonirradiated group. The difference was not significant. The duration of complete remission was similar, remaining at 15% and 16% of patients disease-free at 48 mo, respectively. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) the use of i.t. MTX-DMT alone compares similarly with cranial irradiation plus i.t. MTX-DMT in the incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count less than 50,000 were significantly longer in those without cranial irradiation.

Vindesine, prednisone, and daunomycin in acute lymphoblastic leukemia in relapse.

Patients with resistant or recurrent acute lymphoblastic leukemia were treated with vindesine 3 mg/m2/IV weekly X 4, daunomycin 25 mg/m2/IV weekly X 4, and prednisone 40 mg/m2/PO daily X 28. Seventeen (44%) of 38 evaluable patients achieved complete remission. Fifty-one percent of 31 patients in first relapse achieved complete remission, while only one of five in second or third relapse and neither of two resistant to first induction achieved complete remission. The major toxicity was hematologic. The median duration of complete remission was only 6 weeks and median survival from start of the study, 3 months, with 22% patients remaining alive at 10 months. We conclude that the vindesine, prednisone, and daunomycin combination is no more effective than vincristine, prednisone, and daunomycin in achieving remission of relapsed acute lymphoblastic leukemia patients, and is more toxic than the latter regimen.

Chemoimmunotherapy with levamisole in acute lymphoblastic leukemia.

Patients with acute lymphoblastic leukemia (ALL) who were in two consecutive protocols and in complete remission (CR) with maintenance therapy, were randomized to receive or not receive levamisole. A total of 15 of 55 low-risk patients of protocol 10-LLA-72 with levamisole had relapses, compared with 25 of 54 not receiving levamisole; 67 and 49%, respectively, remain in CR at 48 months (P less than 0.025). In protocol 1-LLA-76, 14 of 91 low-risk patients on levamisole and 25 of 93 patients receiving levamisole had relapses; 78 and 61%, respectively, remain in CR at 36 months (P less than 0.05). Seventeen of 39 high-risk patients (children with a leukocyte count higher than 50,000 and adults) receiving levamisole had relapses compared with 37 of 61 not on levamisole. The DNCB skin test showed at 18 and 24 months a 74 and 85% positivity in the levamisole groups vs. a 38 and 35% positivity in the control group (P less than 0.025). We conclude that levamisole prolongs the duration of CR and survival in low-risk patients with ALL.

Sindrome de Kasabach-Merrit (Tumor vascular trombocitopeniante). / Kasabach-Merrit syndrome (Thrombocytopeniant vascular tumor)

Se comunica un caso de tumor vascular trombocitopeniante (sindrome de Kasabach-Merritt) en un nino de 2 meses de edad. El tumor vascular resulto ser un angioma de tipo juvenil, y los trastornos hematologicos excluyeron la posibilidad de un sindrome de coagulacion intravascular, detectandose solamente una plaquetopenia

Sindrome de Kasabach-Merrit (Tumor vascular trombocitopeniante). / Kasabach-Merrit syndrome (Thrombocytopeniant vascular tumor)

Se comunica un caso de tumor vascular trombocitopeniante (sindrome de Kasabach-Merritt) en un nino de 2 meses de edad. El tumor vascular resulto ser un angioma de tipo juvenil, y los trastornos hematologicos excluyeron la posibilidad de un sindrome de coagulacion intravascular, detectandose solamente una plaquetopenia