Peg-Asparaginase Administration on Day 3 of Remission Induction Accelerates MRD Response in Children with B-Cell Precursor Acute Lymphoblastic Leukemia
А. М. ПоповО. И. БыдановJulia RoumiantsevaSvetlana LagoikoMikhail BelevtsevElena BoyakovaTatiana VerzhbitskayaLiudmila MovchanMaria FadeyevaН В МигальOlga KhlebnikovaNatalia MiakovaЕ. А. СтоляроваOlga StrenevaLarisa FechinaOlga AleinikovaGuenter HenzeAlexander Karachunskiy
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Asparaginase
Acute lymphocytic leukemia
Abstract Thirty‐four children with acute lymphoblastic leukaemia (ALL) in relapse or resistant to initial induction received combination chemotherapy with prednisolone, vincristine, 1‐asparaginase, and daunorubicin. L‐asparaginase was given subcutaneously on alternate days for four weeks and was well tolerated. A complete remission was achieved in 96% of children in relapse and in five out of six children resistant to induction. Remission was achieved without hospitalisation in over 60% of patients. The median duration of subsequent remission was only 13 weeks, but six out of eight children receiving a second course of the drug combination achieved a further remission. We conclude that prolonged 1‐asparaginase therapy in combination with an anthracycline might well be used in initial or consolidation therapy for childhood ALL.
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Asparaginase
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Acute lymphocytic leukemia
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Cyclic administration of methotrexate (MTX) and L-Asparaginase (L-Asp) was utilized either as induction and maintenance chemotherapy or as maintenance chemotherapy alone following induction with other medications in treating 36 children with multiple relapses of acute leukemia. A complete remission rate (CR) of 67% was obtained in children with null-cell acute lymphocytic leukemia (ALL). The average length of remission was greater than four months. One of three patients with T-cell ALL and one of two patients with B-cell ALL achieved CR. In six cases of acute nonlymphocytic leukemia (ANLL), two patients achieved CR. One of two patients with terminal deoxynucleotidyl transferase (TdT) negative myeloblastic transformation of Ph'-positive chronic myelogenous leukemia (CML) obtained a CR lasting 20 weeks. Toxicity secondary to the chemotherapy included bone marrow suppression, hepatic injury, nausea, diarrhea, stomatitis, and allergic reactions to L-Asp. One case of subacute necrotizing leukoencephalopathy was seen.
Acute lymphocytic leukemia
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Abstract 2‐Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol ( 8303) for children with T‐cell acute lymphoblastic leukemia or T‐cell lymphoblastic lymphoma in first relapse. Twenty‐seven patients received one or more courses of DCF at 15 mg/m 2 /day as a 3‐day continuous infusion immediately after achieving a second remission with a four‐drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete re mission was 4 months (range 2‐16+ months) with only two of the 27 patients still in remission at 13 + and 16 + months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T‐cell lymphoblastic malignancies.
Deoxycoformycin
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13 children affected by acute lymphoblastic leukemia in advanced stage of illness received a sequential therapy with daunorubicin and L-asparaginase. During daunorubicin therapy a significant decrease of bone hypercellularity as well as circulating cells occurred, a further cycle with a scarcely myelotoxic drug, L-asparaginase, was administered: a 10/13 (76.9%) remission of the disease was then achieved. This therapeutic trial was well accepted and could be more extensively used in the patients in relapse. A remission lasting between 4 and 28 weeks was observed.
Daunorubicin
Asparaginase
Acute lymphocytic leukemia
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Eleven patients with acute lymphocytic leukemia in relapse were treated with L-asparaginase and cytosine arabinoside (1-beta-D-arabinofuranosylcytosine) in induction therapy and the same drugs plus cyclophosphamide in maintenance therapy. Three patients had complete remissions lasting 6, 16, and 78+ weeks. One patient experienced partial remission and four had decreased bone marrow or peripheral blasts but were not clinically improved. The responses, which were brief, lasted 1-16 weeks with one exception of 78+ weeks. Four patients had allergic reactions to L-asparaginase that were unpredictable with assays of antibodies against L-asparaginase.
Asparaginase
Acute lymphocytic leukemia
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L-Asparaginase,Vincristine,and Prednisonefor Inductionof First Remissionin Acute LymphocyticLeukemi&
SUMMARY L-Asparaginase was added to vincnistine and prednisone for induction of first remission in 815 children with acute lymphocytic or acute undifferentiated leukemia. This cam bination resulted in an overall remission rate of 93%. The addition of L-aspamaginaseto the standard induction megi men using prednisone and vincnistine did not significantly increase the morbidity onmortality rate during the induction period. The most common side effect was transient L-aspam aginase-induced hyperglycemia. The safe administration of L-asparaginase i.m. and the dose efficacy of 6000 I.U./sq m were confirmed. For these reasons, L-aspamaginase should be combined with vincnistine and prednisone far the initial induction of children with acute lymphocytic or acute undif fenentiated leukemia.
Asparaginase
Acute lymphocytic leukemia
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Abstract Six regimens utilizing L‐asparaginase in doses of 6,000 IU/M 2 , 2,000 IU/M 2 , and 500 IU/M 2 in two separate schedules (consecutive and intermittent) along with vincristine and prednisone yielded remarkably similar response rates, approximating 70%, in 306 previously treated children with acute leukemia in relapse. The addition of daunorubicin to one regimen did not alter the response rate. Hypersensitivity reactions occurred in 5% and hyperglycemia in 7%. Lower doses of L‐asparaginase significantly reduced the hypersensitivity rate but no such pattern was noted for hyperglycemia. A history of prior resistance to prednisone and vincristine significantly reduced the response rate.
Daunorubicin
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Asparaginase
Acute lymphocytic leukemia
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Twenty-five patients with acute lymphoblastic leukemia [15 adults and 10 children] received standard treatment in which regular L-asparaginase was replaced for L-asparaginase of prolonged action [PEG-asparaginase]. The drug was administered once in two weeks in a dose 2500 IU/m2 for remission induction and consolidation or as a component of maintenance therapy. It was found that the response to primary PEG-asparaginase treatment or its use in the disease relapses produced the same response as regular L-asparaginase, being superior in convenience and feasibility of outpatient use. Side effects in the form of hypoproteinemia, hepatic toxicity and toxic pancreatitis [in children, 9 and 1 adults, respectively] were moderate and disappeared after 10-20-day discontinuation of the drug.
Discontinuation
Asparaginase
Hypoproteinemia
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Induction chemotherapy
Precursor cell
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Abstract At the present time, it is possible to achieve up to a 95% complete remission in childhood acute lymphoblastic leukemia, using the combination of vincristine and prednisone. Nevertheless, it has not been possible to reproduce these results in the adult. For this reason, a third drug, in this case adriamycin in a low dose, was added to the vincristineprednisone combination in the treatment of adult acute lymphoblastic leukemia (ALL). Complete remission was achieved in 45 of the 50 patients (90%). The median duration of remission was 23 months and the median survival time in this group was 31 months. The complications were minimal and the tolerance was good. From the point of view of our results and others reported in the literature, we consider that the combination of vincristine, prednisone, and adriamycin is a useful method for induction of remission of adult ALL.
Acute lymphocytic leukemia
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