Pediatr Blood Cancer 2012;59:351
LETTER TO THE EDITOR Lack of Prognostic Significance of Absolute Lymphocyte Count After Intensive Induction Therapy in Childhood Acute Lymphoblastic Leukemia
To the Editor: We read with great interest the article by Rabin et al. [1] reporting an independent prognostic significance of absolute lymphocyte count (ALC) in childhood acute lymphoblastic leukemia (ALL), that could refine minimal residual disease (MRD) based risk stratification. Previous work has shown that the function and number of lymphocytes are vital for the patient’s immune system to mount an effective response against cancer cells. The previously published studies on the effect of ALC in childhood ALL mostly used three or four drug induction regimens [1,2]. We hypothesized that with more intensive induction with five or seven drugs; ALC would lose its prognostic value due to more intensive chemotherapy induced leukopenia. We reviewed 136 Jordanian pediatric patients (Arabic ethnicity) with newly diagnosed ALL, age 1–18 years, from 2007 to 2009. The patients were treated at King Hussein Cancer Center on a previously published modified St. Jude total XIII and XV protocols [3], with a median follow up of 35 months (range: 2–54 months). The induction phase included seven drugs (prednisolone, vincristine, daunorubicin, 6-mercaptopurine, cyclophosphamide, cytarabine, and L-asparaginase). Variables analyzed included ALC at diagnosis and on induction days 15 and 36; and other features including white blood cells, age, gender, immunophenotype, cytogenetics, National Cancer Institute (NCI) risk group, and MRD status at end of induction. On day 36 we analyzed ALC as a continuous variable, but it failed to show any prognostic effect on event-free survival (EFS) or overall survival (OS) in the univariate analysis [Hazard ratios (HR) ¼ 0.61, 95%CI: 0.29–1.2, P ¼ 0.19 and HR ¼ 0.82, 95%CI: 0.35–1.9, P ¼ 0.65, respectively]. When compared to the study by Rabin et al., the ALC value of 1.5 109/L has also failed to show any prognostic effect on EFS or OS in the univariate analysis [Hazard ratios (HR) ¼ 2.2, 95%CI: 0.52–9.6, P ¼ 0.27 and HR ¼ 1.2, 95%CI: 0.26–5.5, P ¼ 0.80, respectively]. In contrast to our hypothesis, children treated with the ALL seven-drug induction regimen did not have profound lymphopenia, with a
day 15 median ALC of 1.26 109/L (range: 0–9.45 109/L) and day 36 median ALC of 0.86 109/L (range: 0.10–3.47 109/L). Our cohort confirmed several known prognostic factors in ALL. Age >10 years, positive MRD, T cell phenotype, and NCI high-risk group were significantly predictive of poor EFS. Age >10 years, T cell phenotype and NCI high-risk group were significantly predictive of poor OS. In this study we failed to replicate the previous work that showed the independent prognostic value of ALC during induction therapy in childhood ALL. In contrast to our hypothesis, the reason for the lack of significance was not due to more profound lymphopenia, but could be protocol related or patient population (ethnicity) related. Further studies are needed in children with ALL with different ethnic backgrounds to validate the previous work regarding ALC significance before its incorporation in ALL prognostic models, especially in middle or low-income countries. Khaldoun Alkayed, MD Hadeel Halalsheh, MD Eman Khattab, MD Abdul Rahman Abualruz, MD Abdallah Ibrahim, RN Faris Madanat, MD* Department of Pediatrics King Hussein Cancer Center Amman, Jordan
REFERENCES 1. Rabin KR, Gramatges MM, Borowitz MJ, et al. Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2011 [epub ahead of print]; DOI: 10.1002/pbc.23395 2. De Angulo G, Yuen C, Palla SL, et al. Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: Implications for risk stratification and future studies. Cancer 2008;112:407–415. 3. Halalsheh H, Abuirmeileh N, Rihani R, et al. Outcome of childhood acute lymphoblastic leukemia in Jordan. Pediatr Blood Cancer 2011;57:385–391.
*Correspondence to: Faris Madanat, MD, King Hussein Cancer Center, Pediatric Hematology/Oncology, P.O. Box 1269 Al-Jubeiha, Amman 11941, Jordan. E-mail:
[email protected] Received 21 January 2012; Accepted 6 February 2012
ß 2012 Wiley Periodicals, Inc. DOI 10.1002/pbc.24120 Published online 29 February 2012 in Wiley Online Library (wileyonlinelibrary.com).
