Effect of Chemotherapy on Liver Function During Induction of Remission in Children with Acute Lymphoblastic Leukemia Receiving Standard Protocol

Abstract

Objective: The present study was undertaken to assess liver function (using markers like SGPT, serum bilirubin, prothrombin time, serum albumin) in children suffering from Acute Lymphoblastic Leukemia. Materials & Methods: This study was carried out in the Department of Pediatric Hematology & Oncology, Dhaka Medical College Hospital, Dhaka, over a period 12 months from the day of approval of the protocol. All acute lymphoblastic leukaemia children admitted in Pediatric Hematology & Oncology Department in Dhaka Medical College Hospital and receiving chemotherapy of standard protocol for induction of remission were the study population. A total of outcome variable was hepatotoxicity resulting from chemotherapy given for induction of remission. Result: The mean age of the children was 4.4 years (range 28 years). Males were a bit higher in the series with male to female ratio being 11:9. Liver function tests before therapy revealed that none of the children exhibited raised serum billirubin and only 2(4.5%) children had increased SGPT. However, 50% of the children had raised prothrombin and 43.2% had reduced serum . albumin. Liver function tests after therapy after induction of remission shows that 9(20.5%) children exhibited raised serum billirubin, the proportion of children with raised prothrombin remained almost same as before but the status of serum billirubin improved to some extent. However, proportion of children with raised SGPT was increased to 25%. Comparison of liver function in children after therapy during induction of remission with that before induction did not show any significant difference, except that the serum SGPT was significantly raised during induction of remission (p < 0.001). Conclusion: The study concluded that the current therapy for induction of remission of ALL cases does not produce any toxic effect on liver. Although, enzymes like SGPT take a sharp rise during induction of remission, it is transient and does produce any deleterious effect on liver. DOI: https://doi.org/10.3329/jdmc.v29i1.51168 J Dhaka Med Coll. 2020; 29(1) : 33-37 1. Dr. Meftahul Jannat. Medical Officer , Dept. of Pediatric Hematology and Oncology, Dhaka Medical College Hospital, Dhaka 2. Dr. AKM Amirul Morshed. Professor and head, Dept. of Pediatric Hematology and Oncology, Dhaka Medical College Hospital, Dhaka 3. Dr. Sayeeda Anwer, Professor and Head, Dept. of Pediatrics, Dhaka Medical College Hospital, Dhaka 4. Dr. Shahnoor Islam, Professor, Dept. of Pediatric Surgery. Dhaka Medical College Hospital, Dhaka Correspondence: AKM Amirul Morshed. Professor and head, Dept. of Pediatric Hematology and Oncology, Dhaka Medical College Hospital, Dhaka Email: amirulmorshed@gmail.com Received: 03-01-2020 Revision: 11-01-2020 Accepted: 21-03-2020 Introduction Leukemia is the most common childhood malignancy, accounting for about 41% of all childhood malignancies.1,2 It can be broadly divided into two types: Acute Leukemia and Chronic Leukemia. Acute Leukemia accounts for about 97% of all childhood leukemias.3 Among them Acute Lymphoblastic Leukemia (ALL) is 80% and Acute Non Lymphocytic Leukemia (ANLL) is 20%.3 Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. 4 There are about 13000 new cases of childhood cancer among them near about 2600 ALL in the Bangladesh each year.5 Diagnosing ALL begins with a medical history, physical examination, complete blood count, and blood smears. A bone marrow biopsy is conclusive proof of ALL. A lumbar puncture (also known as a spinal tap) will tell if the spinal column and brain have been invaded. For a patient with ALL, the treatment plan includes multidrug chemotherapy, radiation therapy and bone marrow transplantation. Now a days riskbased protocol is used for ALL patient. The stages of chemotherapy are induction of remission, consolidation, interim maintenance, delayed intensification and maintenance. 6,7 The drugs used during induction of remission are Methotrexate, Cytarabin, Vincristin, Asperginase, Dexamethasonede and 6mercaptopurine. The total duration of treatment is 2 to 2.5 years. 7 The duration of induction of remission is 28 days. In case of relapse the standard treatment is allogenic hematopoietic cell transplantation (HCT) after induction and consolidation.8 The prognosis of Acute Lymphoblastic Leukemia is excellent at initial presentation with complete remission with multidrug induction chemotherapy of up to 98%.9 The current 5 year event free survival rate is 90% .10 Liver is the largest gland in the body. Hepatomegaly is common in leukemia (30-40%), have clinical and biochemical abnormalities in liver function tests sometimes during the illness.1 It is due leukemic liver infiltration. Although hepatic involvement is usually mild and silent at the time of diagnosis, a postmortem study showed liver infiltration in > 95% of Acute Lymphoblastic Leukemia cases.11,12 Massive leukemic cell infiltration of the liver may present as fulminant hepatic failure.11,13 The most important cause of liver involvement in leukemic patient is chemotherapy. Drugs used in the treatment of Acute Leukemia are Methotrexate, Asparginase, Vincristin, Cytarabin, 6-Mercaptopurine and steroid. These drugs have a wide range of hepatotoxicity. Cytotoxic drugs cause rise of transaminases if large amounts are given and serum bilirubin concentration become significantly higher than before intervention as anticancer drugs decrease metabolic activity of liver .14 Liver function test is an important indicator for showing adverse effect of chemotherapy on liver. Commonly available liver function tests are SGPT, serum bilirubin, prothrombin time and serum albumin.15 A study was conducted in Japan among 27 children of ALL. Liver function test was done at baseline and 3 months apart. SGPT was elevated three times of normal in all reports but it became normal after completion of chemotherapy. Serum bilirubin, prothrombin time and serum albumin were normal from starting of chemotherapy up to completion.16 The Cochrane Review database shows liver complications to be common during and soon after treatment for childhood cancer. However, about 8-53% of the childhood cancer survivors developed hepatic late adverse effect after treatment.17 The present study will show liver function abnormalities in leukemic patient receiving induction of remission chemotherapy. Materials & methods This prospective analytical study was carried out in the department of Pediatric Hematology & Oncology, Dhaka Medical College Hospital, Dhaka. Total 44 children with acute lymphoblastic leukaemia patients from 2-10 years receiving chemotherapy for induction of remission in Pediatric Hematology & Oncology Department in Dhaka Medical College Hospital were included in this study. Children suffering from liver disease and parents/guardians were unwilling to allow their children to participate in the study were excluded. After enrollment physical examination was done. With all aseptic precaution 10 ml venous blood were collected from medial cubital vein of patient and was sent for liver function test. Serum albumin was done by Spectrophometer or colorimeter measuring at 630 nm (SPAIN) and general laboratory equipment. SGPT was done by Autoanalyzer Spintech 240 (SPAIN). Serum bilirubin was done by the TBIL Flex reagent cartridge, Cat. No. DF 67 A. Prothrombin time was done by NEOPLASTNE CL PLUS (5) Kits. All tests were done by chief technician of clinical pathology department of Dhaka Medical College Hospital. Second sample was taken after completion of Induction remission phase of treatment of Acute Lymphoblastic Leukemia. Informed written consent was taken from guardian and protocol was passed by ethical board of Dhaka Medical College. Effect of Chemotherapy On Liver Function During Induction of Remission in Children Jannat M et al