Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia: influence on cure rates and risk of second cancer.

نویسندگان

  • Mette Levinsen
  • Elisabeth Ørskov Rotevatn
  • Susanne Rosthøj
  • Jacob Nersting
  • Jonas Abrahamsson
  • Malin Lindqvist Appell
  • Stein Bergan
  • Anne-Grete Bechensteen
  • Arja Harila-Saari
  • Mats Heyman
  • Olafur Gisli Jonsson
  • Jakob Bernhard Cohn Maxild
  • Mikko Niemi
  • Stefan Söderhäll
  • Kjeld Schmiegelow
چکیده

BACKGROUND Previous studies have indicated that patients with thiopurine methyltransferase (TPMT) low activity (TPMT(LA)) have reduced risk of relapse but increased risk of second malignant neoplasm (SMN) compared to patients with TPMT wild-type (TPMT(WT)) when treated with 6 MP maintenance therapy starting doses of 75 mg/m(2)/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m(2)/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol. PROCEDURE We explored the pattern of SMN and relapse in the NOPHO ALL2000 protocol (n = 674) and NOPHO ALL92 protocol (n = 601) in relation to TPMT pheno- and/or genotype. RESULTS The overall risk of any event did not differ significantly between the two protocols. However, in event pattern analyses considering only the patients with TPMT(LA) who experienced relapse or SMN, the risk of SMN versus leukemia relapse was significantly lower in the ALL2000 cohort for patients with a 6MP starting dose <75 mg/m(2)/day when compared to the patients in ALL92 (relapse (n = 11) and SMN (n = 0) in ALL2000 versus relapse (n = 5) and SMN (n = 4) in ALL92, P = 0.03). Furthermore, the 8-year cumulative incidence of relapse for patients with TPMT(LA) was significantly higher in the ALL2000 compared to the ALL92 cohort (19.7% (11.6-33.3%) vs. 6.7% (2.9-15.5%), P = 0.03). CONCLUSION This study indicates that reducing 6MP starting dose for patients with TPMT(LA) may reduce SMN risk but lead to a relapse risk similar to that of patients with TPMT(WT).

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Incidence and Pattern of Childhood Leukaemia in Basrah, Iraq during 2003-2007

Background: Environment of Basrah is seriously contaminated with chemical leukomogens as a result of recent military conflicts. Many studies in the past few years have reported an increase in the incidence of leukemia in Basrah. This study was designed to study the risk and pattern of childhood leukemia in Basrah, Iraq, from 2003 to 2007.Materials and Methods: This hospital-based cancer registr...

متن کامل

Assessment of Thiopurine–based drugs according to Thiopurine S-methyltransferase genotype in patients with Acute Lymphoblastic Leukemia

For the past half century, thiopurines have earned themselves a reputation as effective anti-cancer and immunosuppressive drugs. Thiopurine S-methyltransferase (TPMT) is involved in the metabolism of all thiopurines and is one of the main enzymes that inactivates mercaptopurine. 6-MP is now used as a combination therapies for maintenance therapy of children with acute lymphocytic leukemia (A...

متن کامل

The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette...

متن کامل

Socioeconomic Status and Other Characteristics in Childhood Leukemia

Abstract Background Leukemia is the most prevalent childhood cancer, and Acute Lymphoblastic Leukemia (ALL) constitutes 75% of all cases. Some epidemiological studies have shown a relationship between socioeconomic status (SES) and some childhood cancers. In the present study, an attempt was made to assess socioeconomical status in a case-control study. Materials and Methods In 2010, a c...

متن کامل

Evaluation of bone mineral density in long-term survivors of childhood acute lymphoblastic leukemia

Background: The purpose of this study was to evaluate long-term changes in bone density profile among survivors of childhood acute lymphoblastic leukemia. Patients and Methods: This was a 5 year prospective study comprised of thirty-one survivors of childhood acute lymphoblastic leukemia with a mean age of 11.8 (4.6) years, who completed therapy at least 1 year previously (according to the ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Pediatric blood & cancer

دوره 61 5  شماره 

صفحات  -

تاریخ انتشار 2014