Compliance with a protocol for acute lymphoblastic leukemia in childhood

Abstract

BackgroundRemission rates achieved after the initial treatment of acute lymphoblastic leukemia may be similar in both developed and developing countries, but relapse rates are much higher in the latter. Thus, other reasons are needed, in addition to biological characteristics of the leukemic cells themselves, to explain the unfavorable evolution of patients living in unfavorable socioeconomic and cultural conditions.ObjectiveThe aim of this study was to retrospectively evaluate compliance to an acute lymphoblastic leukemia treatment protocol.MethodsMain abstracted data were: total duration and reasons for interruption of chemotherapy, prescribed doses of 6-mercaptopurine, and median white blood cell and neutrophil counts during the maintenance phase. Interruptions of chemotherapy were considered inappropriate if they did not follow predetermined criteria established in the protocol.ResultsFourteen of 73 patients (19.2%) unduly interrupted chemotherapy by determination of their physicians. The median white blood cell count was higher when compared with the protocol recommendations; the median 6-MP dose was lower than the standard recommended dose. The estimated probability of event-free survival was higher for patients with lower median leukocyte counts and close to those predetermined by the protocol. Event-free survival was also higher for children with a higher percentage of days without chemotherapy due to bone marrow or liver toxicity excluding undue interruptions. In multivariate analysis, both factors remained statistically significant. These results suggest that the intensity of maintenance chemotherapy may not have been enough in some children, to achieve adequate myelosuppression, hence the observation of higher leukocyte counts and none or rare episodes of therapy interruption.ConclusionsCompliance to the therapeutic protocol by both doctors and patients should always be considered in the evaluation of therapeutic failure in acute lymphoblastic leukemia; strict adherence to treatment protocols contributes to better treatment results in acute lymphoblastic leukemia children.

Chemotherapy Delays Are Associated with Inferior Outcome in Acute Lymphoblastic Leukemia: A Retrospective Study from a Tertiary Cancer Center in South India

“…Rate of noncompliance to treatment has varied from 2 to 20% in different series. 7,21,22 Delay in initiation of induction therapy of >7 days after presentation to hospital was seen in 64% patients; however, this delay did not affect survival outcome in our study. In a study by Wahl et al, evaluating the role of weekend delay in initiation of chemotherapy for ALL, there was no significant difference in the measured outcomes of risk of relapse, death, and transfer to the intensive care unit for a mean delay of 4.13 ± 2.40 days for patients admitted on weekends.…”

“…8 In another report by de Oliveira et al, from Brazil, 19% of patients unduly interrupted chemotherapy during maintenance, but, EFS was higher for children with chemotherapy delays due to toxicities, suggesting that the intensity of maintenance chemotherapy may not have been enough to achieve adequate myelosuppression, an indicator of 6-MP efficacy, in patients without delay and toxicities. 21 We did not find any association between delay during maintenance and survival outcomes; however, the number of patients completing maintenance was small and follow-up was short. Thus, though the data are conflicting, largely we conclude that inadvertent delays in treatment delivery will affect long-term outcomes to a variable extent.…”

Rheumatologists’ adherence to a disease activity score steered treatment protocol in early arthritis patients is less if the target is remission

“…Recently, a sub-analysis of the NEO-RACo study showed that physicians’ better adherence to a protocol steered at modified ACR remission [ 17 ] was associated with better clinical outcomes and a lower rate of prescription of biologic DMARD in later years [ 18 ]. Also in other diseases, physicians’ adherence to a treatment protocol was associated with better outcomes [ 19 – 22 ]. It is clear that a stricter DAS target may not be achievable in all patients.…”

Patients’ Adherence in the Maintenance Therapy of Children and Adolescents with Acute Lymphoblastic Leukemia

“…Additional oral co-trimoxazole (CoTR) is given to prevent pneumocystis carinii. Potential determinants of adequate maintenance chemotherapy include pharmacogenetics [2], bioavailability [28], and patient's and family's adherence to daily oral administration as well as the correct dosing by physicians [6,7]. Pharmacogenetics mainly comprises the impact of genetic variation in the thiopurine-Smethyltransferase (TPMT) gene on ALL treatment outcomes and toxicity [2].…”