Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

101 patients with acute leukemia in relapse were treated with 5-azacytidine according to three schedules: Regimen A--300 mg/m2(day divided intravenously at 8 hour intervals for 5 days; Regimen B--750 mg/m2 as a single iv pulse dose administered at 2 to 3 weeks intervals; and Regimen C--300 mg/m2/day by continuous infusion daily for 5 days. Twelve patients achieved a complete remission (CR) and six achieved a partial remission (PR) for an overall 18% response rate. Of 78 patients receiving an adequate trial the response rate was 23%. An average of 1.5 courses and a median of 5 weeks were necessary to achieve a response. The median duration of CR patients was 21 weeks and for PR patients it was 5 weeks. Response rates were 24% for Regimen A, 0 for Regimen B, and 1 of 8 for Regimen C. The CR rate for AML and AMML was 13%. Two of eight AMoL patients achieved a CR. Only 2 of 23 ALL patients responded, one of whom achieved a CR. Toxicity included moderate to severe nausea and vomiting, diarrhea, stomatitis, skin rash, and prolonged myelosuppression. 5-azacytidine has significant activity in the acute nonlymphoblastic leukemias.
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PMID:5-azacytidine in acute leukemia. 8 72

One hundred forty-three children with refractory lymphoblastic and undifferentiated leukemia (ALL/AUL) were treated with cytosine arabinoside (Ara-C) and prednisone (Pred). The dose and duration of Ara-C was escalated during induction depending on the response seen in the peripheral blood and/or bone marrow. For those achieving a remission, Ara-C was also used to determine its maintenance capabilities. Of the 143 children, 79 attained a clinical remission, 45 having a complete bone marrow remission and 34 having a partial remission. Maintenance of remission with twice weekly Ara-C was short and did not appear to depend on the amount of Ara-C given during induction. The major toxicity of Ara-C was myelosuppression.
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PMID:Usefulness of cytosine arabinoside (NSC-63878) and prednisone (NSC-10023) in refractory childhood lymphoblastic leukemia. 106 43

An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.
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PMID:Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: a report from the Childrens Cancer Study Group. 173 17

More than 50% cure can be obtained with allogeneic bone marrow transplantation (BMT) when patients are transplanted in first remission of AML and ALL or chronic phase of CML. On the other hand, considerable progress has been made recently in treating acute leukemia with chemotherapy. Recent studies of intensive chemotherapy in adults with AML report approximately 40-50% 3-year disease-free survival (DFS). Accordingly, several prospective randomized clinical trials have been conducted on the use of BMT versus intensive chemotherapy in the treatment of AML. Significant differences in DFS were found only in a few studies though the results of BMT appear to be comparable or superior to chemotherapy. Therefore, the overall advantage of BMT in first remission AML is smaller than expected. We should know not whether to transplant or to perform chemotherapy, but rather whether to transplant in first remission or to perform chemotherapy first and reserve transplantation as salvage therapy. Recently acute promyelocytic leukemia has been successfully treated with differentiation therapy using all-trans retinoic acid. Low-dose aclarubicin has also been reported to be effective as differentiation therapy in some patients with myelodysplastic syndrome and atypical AML. With the advance of molecular biology of cytokines, several of them are now available for clinical use. G-CSF, GM-CSF and M-CSF are potent stimulators for the granulocyte-macrophage production; they are very effective for accelerating hematologic recovery after chemotherapy-induced myelosuppression or BMT. Interferon-alpha (IFN-alpha) has been used in the several studies. Furthermore, Ph chromosome positivity can be reduced with long-term administration of IFN-alpha; Ph-positive clone can be undetectable in some patients. Thus, IFN-alpha will be the choice of treatment for CML even if BMT is planned.
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PMID:[New trends in the treatment of leukemia]. 177 64

Knowing the good penetration of systemic HDara-C into the CNS, we treated with this approach overt meningeal leukemia, either isolated or with bone marrow (BM) disease, in 31 adults: 18 ALL, 4 ANLL, 1 lymphoid blast crisis of CGL (LBC-CGL), and 8 non-Hodgkin's lymphoma (NHL). Treatment consisted of Ara-C, 3 g/m2 i.v. q 12 h, by 3 h infusion for 8 doses, followed by 4 doses at day 21. Complete remitters received consolidation with four monthly 4-dose courses of HDara-C. Additional multidrug consolidation and direct CNS therapy with intrathecal (i.t.) methotrexate (MTX) or Ara-C +/- cranial RT was administered to the 11 remitters last treated. Twenty of 31 patients (64%) achieved CR: 10/10 with isolated meningeal leukemia and 10/21 with concurrent CNS and BM disease. Of the remaining 11 patients, 8 had cerebrospinal fluid (CSF) clearing with persistent BM disease. In all cases but one CNS symptoms resolved promptly. CR median duration was 6 months (range 2 to 20). The main toxicity was myelosuppression requiring intensive support. There was no neurologic toxicity. These results show that systemic HDara-C is highly effective in acute leukemias and NHL with CNS involvement, and suggest the utility of this regimen for sanctuary chemoprophylaxis in patients at high risk for CNS disease.
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PMID:Central nervous system (CNS) leukemia: the role of high dose cytarabine (HDAra-C). 271 52

Acute lymphoblastic leukemia accounts for 80% of leukemia in children. The exact cause is unknown, but some genetic, immunologic, viral, and environmental factors have been implicated. Symptoms at the time of diagnosis frequently include fever, bleeding, fatigue, and irritability. Initial white blood cell count and patient age at diagnosis are the most reliable indicators of prognosis. Acute lymphoblastic leukemia is a heterogenous disease. Lymphoblast morphology, immunologic markers, enzyme abnormalities, cytogenetic findings, and staining characteristics in conjunction with clinical characteristics allow classification into risk groups. Appropriate therapy for each risk group is based on these parameters. Combination chemotherapy administered alone or with additional chemotherapy or radiotherapy to sanctuary sites is the principal modality for treatment of ALL. Optimal therapy for relapse has not yet been determined, but for patients with appropriate donors, allogeneic bone marrow transplant is promising. Common complications of chemotherapy include tumor lysis syndrome, myelosuppression, and other problems such as gastrointestinal toxicity, neurotoxicity and cardiac toxicity. Significant late effects of chemotherapy include neurological impairment ranging from learning problems to leukoencephalopathy and a possible increased risk of second malignancy. Complete remission is achieved in 95% of children with acute lymphoblastic leukemia, and more than 55% will continue to be in complete remission at five years. Optimal CNS prophylaxis, effective treatment of relapse, and adjustment of therapy to minimize acute and late adverse effects are a continuing challenge. With improved understanding of biologic factors, and development of more specific therapy for each subgroup, children with acute lymphoblastic leukemia should enjoy a better long term outcome.
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PMID:Childhood acute lymphoblastic leukemia. 328 Nov 3

The effect of folic acid supplements on 6-mercaptopurine remission maintenance therapy in lymphoblastic leukaemia (ALL) was investigated in a retrospective longitudinal study of 10 children. Red cell concentrations of 6-thioguanine nucleotide, a cytotoxic metabolite of 6-mercaptopurine, were measured and the peripheral neutrophil count was used as an index of myelosuppression. During the control period of the study there were significant correlations between 6-mercaptopurine dose and 6-thioguanine nucleotide concentration (rs = 0.59, P less than 0.0005) and between 6-thioguanine nucleotide concentration and the peripheral neutrophil count at 14 days (rs = 0.58, P less than 0.0005). These relationships were absent when the same children were subsequently taking folate supplements. Also when taking folate supplements the children tolerated significantly more 6-mercaptopurine (P less than 0.005) for a significantly longer time (P less than 0.005) before neutropenia developed. There was no significant difference in red cell 6-thioguanine nucleotide concentration in the absence and presence of folate supplements. These findings suggest that folate supplements may interfere with remission maintenance therapy in ALL.
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PMID:The effect of folate supplements on 6-mercaptopurine remission maintenance therapy in childhood leukaemia. 345 41

N4-Palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) was administered p.o. to 199 patients with acute leukemia, myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD). Of 76 patients with AML, 11 achieved complete remission (CR) and 7 achieved partial remission (PR). Of 8 patients with ALL, 2 achieved CR and 1 achieved PR. Of 3 patients with blast crisis of MPD, 1 achieved CR. CR was reached with PL-AC at 100-900 mg/day after 5-98 (median 26) days. Of 50 patients with MDS, 2 achieved CR, 2 showed good response and 7 partial response. Response was reached with 100-400 mg/day after 13-122 (median 32) days. Improvement of polycythemia vera was observed in 6 of 13 patients, and reduction of thrombocytosis was observed in 20 of 23 patients with essential thrombocythemia and myelofibrosis. Of 18 patients with CML, 1 achieved CR. Major side effects were GI toxicities and myelosuppression. In spite of the disadvantages of the oral form of the drug, such as unpredictable absorption, PL-AC may be useful in the treatment of acute leukemia, especially that of the aged, a condition for which intensive chemotherapy is not always indicated, and MDS, which do not necessarily require admission to a hospital.
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PMID:[A phase II study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PL-AC) in patients with acute leukemia and myelodysplastic syndromes. Cooperative Study Group for PL-AC]. 361 59

A Phase II study of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was conducted in 162 patients with various hematological malignancies in a multi-institutional cooperative study. THP was given intravenously at a dose of either 10-30 mg/body for 3-5 consecutive days or 40-60 mg/body at 3-week intervals. Of 22 patients with AML, complete remission (CR) was observed in 2 patients and partial remission (PR) in 2. Of 18 patients with ALL, CR was observed in 5 and PR in 3. Of 68 patients with NHL, CR was observed in 11 and PR in 22. Of 8 patients with HD, CR was observed in 4 and PR in 2. One CML case showed CR and one ATL case showed PR. PR was noted in one of 2 patients with mycosis fungoides. Overall remission rate was 43.1% (CR 23 cases and PR 33 cases). The predominant toxicity was myelosuppression. Leukopenia (less than 4,000/mm3) was noted in 67 (77.6%) and thrombocytopenia (less than 10 X 10(4)/mm3) in 24 (27.0%). Nausea/vomiting and anorexia were common, and were observed in 61 (43.3%) and 65 (46.1%) cases, respectively. Hair loss and cardiotoxicity were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for various hematological malignancies including acute leukemia and malignant lymphoma.
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PMID:[A phase II study of (2''R)-4'-0-tetrahydropyranyladriamycin (THP) in patients with hematological malignancies. THP Study Group]. 394 12

Thirty patients with advanced acute leukemia and lymphoma were treated with the sequential combination of high dose ARA-C (HiDAC 3 gm/m2 infused i.v. over 3 h at 0, 12, 24, 36 h) and asparaginase (ASP 6.000 IU/m2 i.m. at hour 42). The sequence was given on day 1 and 8 irrespective of the degree of myelosuppression. Of 22 patients with leukemia there was only one who was absolutely refractory to therapy. Complete remission was induced in 3 patients with ANLL (30%) and in 3 with ALL (30%). Three patients became hypoplastic but recovered with blasts and 12 died from infection, complicated by intracranial hemorrhage in 3, during hypoplasia. Of 8 patients with lymphoma, 2 were clearly refractory to therapy, one died from sepsis and the remaining 5 all entered remission (2 CR + 3 PR, 62%). Activity of HiDAC/ASP against CNS disease is suggested by the clinical response seen in patients with overt meningeal or intracerebral involvement. Toxicity associated with HiDAC/ASP was mainly hematologic. All but one patient experienced hypoplasia and severe pancytopenia; documented infections and major hemorrhages occurred in 80 and 20% of patients respectively. We conclude that HiDAC/ASP is a regimen with definite activity against acute leukemia and lymphoma including CNS disease. Alternate treatment schedules should be explored in order to reduce marrow toxicity.
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PMID:Sequential combination of high dose ARA-C (HiDAC) and asparaginase (ASP) for the treatment of advanced acute leukemia and lymphoma. 647 2


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