Chemotherapy of Acute Leukemia in Childhood
Donald J. FernbachKenneth M. GriffithM. E. HaggardThomas HolcombW. W. SurowTeresa J. ViettiJoan Windmiller
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Abstract:
THE Pediatric Division of the Southwest Cancer Chemotherapy Study Group has reported on the effectiveness of cyclophosphamide (Cytoxan) in inducing remissions in children with advanced acute leukemia.1 , 2 These preliminary results were particularly encouraging because cyclophosphamide, an alkylating agent of the mustard group, was found to act independently of other antileukemic drugs: steroids; 6-mercaptopurine (Purinethol, a purine antagonist); and methotrexate (a folic acid antagonist). It is also assumed to act with no crossresistance to vincristine (a periwinkle alkaloid). Subsequently, 137 patients with untreated acute leukemia were admitted to a Cooperative study to determine the effectiveness of cyclophosphamide at the beginning of . . .Keywords:
Folic Acid Antagonists
Mercaptopurine
Nitrogen mustard
Acute lymphocytic leukemia
Thirty-five previously untreated children suffering from acute lymphocytic leukemia were enrolled in sequence between April 1972 and October 1973 and randomly put on drug protocol 721, consisting of three phases; induction with vincristine and predonisolone, prophylactic intrathecal medication with methotrexate, and maintenance: high-dose infusion of MTX (Group A) or sequential-complementary regimen (Group B). Complete marrow remission (M1) was achieved in the 35 cases (100%). During the phase of prophylactic intrathecal medication, two patienls had bone marrow relapses and one had CNS-leukemia. Of the 33 who had continuing marrow remission, 17 were randomly selected into Group A and 16 into Group B. In Group A, nine patients (47%) remained in complete remission over three years, in contrast with four patients in Group B. CNS-leukemia occurred in 10 children in Group B and in four children in Group A. Therapy with high-dose infusion of MTX (Group A) was more effective for remission maintenance in children with acute lymphocytic leukemia than those with sequential-complementary regimen (p<0.05). No significant toxi-cities occurred in either of the regimens, and these maintenance regimens did not require any unusual supportive care.
Regimen
Acute lymphocytic leukemia
Maintenance therapy
Childhood leukemia
Group B
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In children treated for acute lymphoblastic leukemia (ALL), catch-up growth occurs after cessation of therapy and not during maintenance therapy. In this study we investigated whether this inhibition of catch-up growth during maintenance treatment is attributable to the influence of chemotherapy or to the influence of corticosteroids.Forty-six children treated for ALL were included in the study. In 27 patients maintenance therapy comprised vincristine (VCR), prednisone (Pred), or dexamethasone (Dexa) alternated with 6-mercaptopurine (6-MP) and methotrexate (MTX) and 19 patients received maintenance therapy with 6-MP and MTX only. Treatment did not include cranial irradiation.Statural growth during maintenance treatment was comparable in both groups over the study period of 1.5 years.Chemotherapy with 6-MP and MTX, and not corticosteroids, is the main factor that prevents catch-up growth from occurring during maintenance therapy for ALL.
Maintenance therapy
Acute lymphocytic leukemia
Mercaptopurine
Maintenance dose
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Twenty-five patients with CNS metastases of choriocarcinoma were treated with a regimen incorporating etoposide, methotrexate, and actinomycin (EMA) alternating weekly with vincristine and cyclophosphamide (CO). The dose of methotrexate was increased to 1 g/m2. Eighteen patients presented with CNS metastases, or developed them on inappropriate treatment started elsewhere. Following EMA/CO chemotherapy, three patients died within the first 3 weeks, one is alive with active disease, one died with drug resistance, and 13 (72%) patients are surviving disease-free. Two of seven patients (29%) who developed CNS metastases on treatment with EMA/CO or relapsed after EMA/CO are disease-free after additional chemotherapy and surgery. The contribution toward survival of the craniotomy in six of 18 patients treated initially or early with EMA/CO remains unclear, but was crucial to those patients with drug resistance.
Regimen
Chorioepithelioma
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Mercaptopurine
Regimen
Acute lymphocytic leukemia
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Mercaptopurine
Acute lymphocytic leukemia
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Acute lymphocytic leukemia of childhood has, in its responsiveness to drugs, served as a model system wherein certain principles of cancer chemotherapy have been established. Studies have been made during florid disease, and during complete remission when the leukemia is below the threshold of reliable clinical detection. Different drugs, singly or in combination, and different schedules of treatment have been found in controlled clinical trials to have distinctive effects during these two stages of leukemia. Induction treatments, maintenance treatments, inducer dosing during maintenance and reinduction treatments for the subsequent relapses have all been evaluated. Methotrexate and 6-mercaptopurine in optimal schedules . . .
Acute lymphocytic leukemia
Mercaptopurine
Maintenance therapy
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The long-term results of treatment of 32 children with acute lymphocytic leukemia, treated with protocol HIM-TSM, are reported. Induction therapy with prednisone and vincristine, gave 94% of complete remissions. Only 25 patients were evaluable for the maintenance therapy study. They reveived two courses of cyclic intensive chemotherapy with seven drugs (methotrexate, 6-mercaptopurine, cyclophosphamide, prednisone, vincristine, intrathecal methotrexate and hydrocortine, daunomycin and citosine-arabinoside) at high doses and thereafter, cyclic MTX 6MP and CP and periodic VCR and Pred. Median duration of complete remission was 28 months and 40% of the patients had initial relapse in central nervous system (median time of presentation of CNS relapse was 25 months). On Feb., 1976, 56% of the children are alive but 24% of them have had at least one relapse and now, are again in remission. Eight cases (32%) have never relapsed, from 42 to 58 months after remission was obtained (median of 46 months) and they are now off any antileukemic therapy for 11 to 22 months (median of 16 months). These long-term results are compared with those obtained with a previously reported protocol (HIM-TMI). No significant progresses were seen in the Protocol HIM-TSM, but both studies showed very good results for this country. More intensive systemic chemotherapy and CNS prophylaxis are needed. This has been taken into account in a more recent study (Protocol HIM-06) and the preliminary results are encouraging. Fourteen patients from these studies and several other children, all of them with more than 42 months of continuous remission and off therapy, have in our experience, a high chance of being cured.
Mercaptopurine
Maintenance therapy
Acute lymphocytic leukemia
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Acute lymphocytic leukemia
Asparaginase
Mercaptopurine
Maintenance therapy
Total body irradiation
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Twenty-two patients with postmastectomy lymphangiosarcoma have been seen at M. D. Anderson Hospital during the past 20 years. Of these, 13 received chemotherapy, either regionally, systemically, or both. Six patients were treated with regional chemotherapy using either methotrexate alone, a combination of melphalan, nitrogen mustard, and actinomycin D, or a combination of melphalan with nitrogen mustard or actinomycin D; 3 achieved a partial or complete response. Eleven patients received 19 trials of systemic chemotherapy; one complete and seven partial responses were observed, giving an overall response rate of 42% (8/19). Responses occurred with 5-fluorouracil, methotrexate, a combination of vincristine, actinomycin D, and cyclophosphamide, and a combination of Adriamycin and dacarbazine with or without vincristine. The median survival time of the six patients who responded to at least one chemotherapeutic trial was 26.5 months compared with four months for the five patients who failed to respond. These data indicate that chemotherapy may play a significant role in the treatment of patients with this rare but distinctive tumor.
Melphalan
Nitrogen mustard
Dacarbazine
Combination chemotherapy
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THE Pediatric Division of the Southwest Cancer Chemotherapy Study Group has reported on the effectiveness of cyclophosphamide (Cytoxan) in inducing remissions in children with advanced acute leukemia.1 , 2 These preliminary results were particularly encouraging because cyclophosphamide, an alkylating agent of the mustard group, was found to act independently of other antileukemic drugs: steroids; 6-mercaptopurine (Purinethol, a purine antagonist); and methotrexate (a folic acid antagonist). It is also assumed to act with no crossresistance to vincristine (a periwinkle alkaloid). Subsequently, 137 patients with untreated acute leukemia were admitted to a Cooperative study to determine the effectiveness of cyclophosphamide at the beginning of . . .
Folic Acid Antagonists
Mercaptopurine
Nitrogen mustard
Acute lymphocytic leukemia
Cite
Citations (30)