scholarly journals Continuation Therapy Epoch

2020 ◽  
Author(s):  
Keyword(s):  
1978 ◽  
Vol 133 (1) ◽  
pp. 28-33 ◽  
Author(s):  
A. Coppen ◽  
K. Ghose ◽  
S. Montgomery ◽  
V. A. Rama Rao ◽  
J. Bailey ◽  
...  

SummaryThirty-two patients who had responded to amitriptyline (150 mg daily) when suffering from a depressive illness were allocated either to receive placebo or to remain on the same medication for one year.Plasma concentrations of the drug were regularly estimated. There was no correlation between plasma concentration and subsequent residual affective morbidity. In spite of considerable encouragement, three of the patients did not take the prescribed amitriptyline and they all relapsed. Five out of sixteen patients who received placebo relapsed. None of the patients who continued to take amitriptyline relapsed.It is emphasized that the patients studied were selected, inasmuch as they were apparent responders to amitriptyline. It is concluded that this group of patients should continue to be treated with antidepressant medication for eight months after apparent recovery, and care should be taken to ensure the patients' compliance.


Author(s):  
Evgeny K. Beltyukov ◽  
Valery A. Shelyakin ◽  
Veronika V. Naumova ◽  
Alexander V. Vinogradov ◽  
Olga G. Smolenskaya

Background: Biologicals use in severe asthma (SA) is associated with problem of targeted therapy (TT) availability. Ensuring availability of biologicals can be resolved within the territorial compulsory medical insurance program (TCMIP) in day-stay or round-the-clock hospital. Aims: development and implementation of program for introduction of immunobiological therapy (IBT) for SA in Sverdlovsk Region (SR). Materials and methods: Program for introduction of IBT for SA was developed in SR in 2018 to provide patients with expensive biologicals within the TCMIP. Program includes: SA prevalence study in SR; practitioners training in differential diagnosis of SA; organization of affordable therapy for patients with SA; register of SA patients сreation and maintenance; patients selection and management of patients with SA in accordance with federal clinical guidelines. Results: Atopic phenotype in SA was detected in 5%, eosinophilic - in 2.3% of all analyzed cases of asthma (n=216). Practitioners of SR were trained in differential diagnosis of SA. The orders of the Ministry of Health of SR were issued, regulating the procedure for referring patients with SA to IBT, a list of municipal medical organizations providing IBT in a day-stay or round-the-clock hospital; approved regional register form of SA patients requiring biologicals use; ungrouping of clinical and statistical groups of day-stay hospital was carried out depending on INN and dose of biologicals; patients with SA are selected for TT and included in the regional register. Initiating of TT in round-the-clock hospital and continuation therapy in day-stay hospital provides a significant savings in compulsory medical insurance funds. Conclusions: introduction of IBT for SA in SR is carried out within framework of developed program. Principle of decentralization brings highly specialized types of medical care closer to patients and makes it possible to provide routine medical care in allergology-immunology profile in context of restrictions caused by COVID-19 pandemic.


Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1316-1323 ◽  
Author(s):  
VM Whitehead ◽  
MJ Vuchich ◽  
SJ Lauer ◽  
D Mahoney ◽  
AJ Carroll ◽  
...  

Abstract Hyperdiploidy (greater than 50 chromosomes, or a DNA index greater than 1.16) confers a favorable prognosis in B-lineage acute lymphoblastic leukemia of childhood. Children with B-lineage acute lymphoblastic leukemia whose lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates (MTXPGs) in vitro experience a better event-free survival than those whose lymphoblasts do not (Blood 76:44, 1990). Lymphoblasts from 13 children with hyperdiploidy (greater than 50 chromosomes) accumulated high levels of MTX-PGs (1,095 and 571 to 2,346 pmol/10(9) cells [median and 25% to 75% intraquartile range]). These levels were higher than those in B-lineage lymphoblasts from 19 children with other aneuploidy (326 and 159 to 775 pmol/10(9) cells) and 15 children with diploidy (393 and 204 to 571 pmol/10(9) cells) (P = .0015). Chromosomal trisomies in hyperdiploid cases were highly nonrandom. Chromosome 9 was not one of the chromosomes involved in trisomies, even though this chromosome contains the gene for folate polyglutamate synthetase, which is the enzyme required for MTXPG synthesis. The correlation between MTXPG level and percentage of S- phase cells was weak, suggesting that increased levels of MTXPGs could not be attributed to elevated proportions of cells in active DNA synthesis. The ability of hyperdiploid lymphoblasts to accumulate high levels of MTXPGs may increase their sensitivity to MTX cytotoxicity, accounting in part for the improved outlook for hyperdiploid patients treated with regimens that emphasize MTX as a primary component of continuation therapy.


2000 ◽  
Vol 18 (6) ◽  
pp. 1285-1294 ◽  
Author(s):  
Donald H. Mahoney ◽  
Jonathan J. Shuster ◽  
Ruprecht Nitschke ◽  
Stephen Lauer ◽  
C. Philip Steuber ◽  
...  

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m2 plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1,000 mg/m2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years. RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.


1973 ◽  
Vol 3 (1) ◽  
pp. 5-17 ◽  
Author(s):  
R. H. S. Mindham ◽  
C. Howland ◽  
Michael Shepherd

SynopsisA double-blind clinical trial has been carried out to ascertain whether patients making a good recovery from depressive illness with tricyclic antidepressant medication derive any benefit from continuation of therapy with the same drug at a lower dose level. Of the 92 patients who entered the trial significantly fewer on active treatment relapsed during the six-month trial period: 22% as compared with 50% of patients receiving placebo. Patients with residual symptoms on entry to the trial derived more benefit from continuation therapy than patients who had made a complete recovery. The findings relate to a six-month trial period only, and any possible advantage of continuation therapy over a longer period remains uncertain.


Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 602-609 ◽  
Author(s):  
PD Sadowitz ◽  
SD Smith ◽  
J Shuster ◽  
MD Wharam ◽  
GR Buchanan ◽  
...  

Abstract Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6- mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty- eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone.


1994 ◽  
Vol 12 (7) ◽  
pp. 1383-1389 ◽  
Author(s):  
B Camitta ◽  
D Mahoney ◽  
B Leventhal ◽  
S J Lauer ◽  
J J Shuster ◽  
...  

PURPOSE To determine the potential efficacy and toxicity of intravenous (i.v.) methotrexate (MTX) and mercaptopurine (MP) as postremission intensification treatment for children with B-lineage acute lymphoblastic leukemia (ALL) at higher risk to relapse. PATIENTS AND METHODS Eighty-three patients (age 1 to 20 years) with higher-risk B-lineage ALL were entered onto this protocol. Following standard four-drug remission induction, 80 patients received 12 intensive 2-week cycles of MTX/MP: MTX 200 mg/m2 i.v. push, then 800 mg/m2 i.v. 24-hour infusion on day 1; MP 200 mg/m2 i.v. in 20 minutes, then 800 mg/m2 i.v. 8-hour infusion day 2; MTX 20 mg/m2 intramuscularly day 8; and MP 50 mg/m2 by mouth days 8 to 14. Age-based triple intrathecal therapy (MTX, hydrocortisone, and cytarabine) was administered for CNS prophylaxis. Continuation therapy was weekly MTX/MP (as on days 8 to 14) for 2 years. RESULTS Eighty-one patients (98%) entered remission. There were 28 relapses (marrow, n = 11; marrow and CNS, n = 2; isolated CNS, n = 9; testes, n = 5; ovaries, n = 1). No overt relapse occurred during the intensive phase of therapy. The event-free survival (EFS) rate at 4 years is 57.4% +/- 9.1% (SE). Hematologic, mucosal, and infectious toxicities were seen in 12%, 9%, and 5% of intensive MTX/MP courses, but were generally mild. CONCLUSION Combined data from this and our previous trial suggest that intensive MTX/MP may produce long-term disease-free survival in 70 to 75% of children with B-lineage ALL. In comparison to other intensive regimens, intensive MTX/MP is easy to administer, effective, and relatively nontoxic. If patients at risk for failure of MTX/MP can be identified prospectively, more aggressive regimens could be restricted to this smaller (25% to 30%) cohort.


1998 ◽  
Vol 16 (2) ◽  
pp. 522-526 ◽  
Author(s):  
J Laver ◽  
M Amylon ◽  
S Desai ◽  
M Link ◽  
M Schwenn ◽  
...  

PURPOSE Contemporary chemotherapy has significantly improved the event-free survival (EFS) among patients with T-cell disease. However, myelosuppression has been a significant adverse effect of this approach. In this study, we assessed the impact of r-metHu granulocyte colony-stimulating factor (G-CSF) on the period of neutropenia, number of days of hospitalization, and delays in subsequent administration of chemotherapy in a cohort of patients with T-cell leukemia (T-ALL) or advanced stage lymphoblastic lymphoma (ASLL). PATIENTS AND METHODS This open-label, randomized trial incorporated r-metHuG-CSF into the induction and two consecutive continuation-therapy cycles of our intensive program for T-cell malignancies. In the induction phase, r-metHuG-CSF was given after two different combinations of chemotherapy, one of which included vincristine, prednisone, cyclophosphamide, and adriamycin and the other a continuous infusion of high-dose ara-C and L-asparaginase. In the two continuation-therapy cycles, r-metHuG-CSF was given following the combination of vincristine, adriamycin, prednisone, and 6-mercaptopurine (MP) and after continuous infusion of high-dose cytarabine (ara-C). RESULTS Fifty-six patients with T-ALL and 33 with ASLL were enrolled onto study from April 1994 to December 1995. Our data show no significant difference in number of days of absolute neutrophil count (ANC) less than 500/microL, hospitalizations, or delays in therapy in the induction phase. However, in the continuation-therapy phase the number of days of ANC less than 500/microL was significantly shorter (P = .017) on the G-CSF-arm without significantly affecting the number of days of hospitalizations or delays in therapy. CONCLUSION r-metHuG-CSF did not significantly affect the period of neutropenia, hospitalization, or delays in therapy in the induction phase, whereas in the two cycles of continuation therapy, it significantly shortened the period of neutropenia.


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