Clinical adverse effects of Chemotherapy protocolusing 6- Mercaptopurine in Iraqi patients with Acute Lymphocytic Leukemia during Maintenance Phase

 

Mohammed Khudair Hasan^1, Mowafaq Mohammed Ghareeb², Bassam Francis Mate³,

Qutaiba Ahmed Ibrahim Al Khames Aga⁴

¹Department of Clinical Pharmacy, College of Pharmacy, University of Baghdad, Iraq.

²Pharmaceutics Department, College of Pharmacy, University of Baghdad, Iraq.

³Department of Hematology, Baghdad Teaching Hospital, Medical City Complex, Iraq.

 

ABSTRACT:

Objective: The study was  aimed to find out the main clinical adverse effect of acute lymphocytic leukemia chemotherapy protocol. Acute lymphoblastic leukemia patients require long time continuation therapy to reduce the duration of moderately intensive chemotherapy to 12 to 18 months or less have given poor results in both children and adults. Thus, patients treated for two years or more. The most frequent adverse reaction to chemotherapy protocolis myelosuppression, hepatotoxicity, Hyperuricemia and hyperuricosuria, and immunosuppressive effect. Material and Methods:  Sixty ALL patients and sixty healthy subjects selected to participate in this study. The subjects involved two groups; group A Includes 60 patients with acute lymphoblastic leukemia on maintenance (continuation) phase receiving 6-mercaptopurine at least for a two-month duration on daily doses based on body surface area. The total number of patients was 60 (40 male and 20 Female); among them, 44 were less than 18 years old (mean ± SD was 9.348 ± 5.131), and 16 were more than 18 years old (mean ± SD was 29.058 ± 7.9173); and, group B Includes 60 healthy subjects' adults and children without any medical illnesses. Of this group there were (40 male and 20 Female), among them, 42 were less than 18 years old (mean ± SD was 8.926 ± 5.326), and 18 were more than 18 years old (mean ± SD was 28.645 ± 7.482). The mean ± SD of months using 6-MP was 13.94 ± 9.49 months, the mean ± SD of 6-MP dose for patients less than 18 years old was 43.77 ± 16.01 and for patients more than 18 years old was 88.23 ± 30.76. The mean ± SD of weight of patients less than 18 years old was 35.45 ± 9.66 and for patients more than 18 years old was 65.423 ± 13.654. Patients characteristics (such as age, weight, gender, B.S.A, date of the beginning maintenance phase, date of blood sampling, adverse effects of 6-mp and presence of other diseases obtained through patient interview. Complete blood count (Hb, W.B.C count, R.B.C count, platelets count, absolute neutrophils count), liver function tests (AST, ALT, ALP and total serum bilirubin T.S.B), renal function tests (serum creatinine and blood urea) and blood sugar concentration obtained at the same day of blood sampling for patient and control subjects were done. Results: There was no significant change between the male and female in patient and control subjects (p= 0.8675) in regard to age and gender. The main adverse effect of the protocol was seen with higher incidence of jaundice, fever, decreased appetite, unusual tiredness or weakness, headache, stomach pain, dark urine and pale skin. Whereas, the fewer incidences among the common adverse effect are hemoptysis, painful or difficult urination, diarrhea, nausea and vomiting, chest pain and sore throat. The mean serum creatinine and BUN increased significantly in patients ≤ 18 year (mean ± SD 0.97 ± 0.13) (mean ± SD 24.44 ± 6.92) and > 18 year (mean ± SD 0.98 ± 0.12) compared to the control subjects (0.64 ± 0.19 and 0.64 ± 0.22) (14.87 ± 3.64 and 15.21 ± 0.22) consequently. The mean serum ALT, AST, ALP and T.S. bilirubin increased significantly in the patients compared to the control subjects (60.66 ± 14.26 vs. 31.52 ± 5.51), (45.71 ± 23.04 vs. 11.48 ± 7.05), ALP (99.63 ± 38.21 vs. 60.61 ± 19.52) and (1.61 ± 0.58 vs. 0.40 ± 0.14 mg/dl) consequently. The mean RBS increased significantly in the patients compared to the control subjects (166.93 ±87.56 vs.104.45 ± 16.74). The mean RBC and WBC count decreased significantly in the patients compared to the control subjects (3.68 ± 0.66 vs. 4.37 ± 0.94) and (3.48 ± 1.62 vs. 7.26 ± 1.70). The absolute neutrophil and absolute Lymphocyte count/μm3 were significantly less for patients than for control (1.36 ± 1.12 vs. 4.43 ± 1.27) and (0.81 ± 0.37 vs. 2.18 ± 0.64). The platelets counts *103 were significantly decreased in patients comparing to the control subjects(213.81 ± 83.78 vs. 344.07 ± 46.34). Hemoglobin mean were significantly less in patients comparing to the control subjects (11.43 ±1.51 vs. 14.55 ± 1.17). Conclusions: In this study, our patients were higher in children and young study population with a male: female 2:1. In addition to the leukopenia, the adverse effect was recorded from the patients was jaundice, fever, decreased appetite, and weakness. The less commonly documented adverse effects of 6-MPhave reported from our study was joint pain, heartburn, sores, and ulcer. There is an importance of long-term follow-up, especially for those diagnosed at a young age. Renal involvement is not uncommon in ALL. Renal involvement can present as an elevation in renal function test (creatinine and BUN). Although hematological malignancies commonly involve the liver, they rarely cause clinically significant hepatic disease. Metabolic disorders are common in ALL. Insulin resistance is emerging as a concern for long-term ALL survivors, as is diabetes. Diabetes, hypertension and cardiovascular events must evaluate.

 

 

INTRODUCTION:

Reactive oxygen species (ROS) are the major factors for aging and death of cells¹. In the body, they may generate from several metabolic processes, ultraviolet radiation and other biochemical reactions². These ROS and free radicals produced from oxidative stress may cause degradation of DNA, lipids, proteins and carbohydrates and cause many serious diseases like cancer and diabetes³. Antioxidants have the capability of scavenging various ROS species like hydroxyl radicals (OH), superoxide anion radicals (O₂^-) and hydrogen peroxide (H₂O₂) and thus prevent cells from oxidative degradation⁴.

 

Antioxidants obtained from natural sources like fruits, vegetables and other dietary sources play a significant role in reducing oxidative stress by scavenging free radicals⁵ and keep balance among antioxidants and oxidants⁶. These compounds show antioxidant activity by terminating the chain reaction in lipid oxidation⁷ and chelating metal ions⁸.

 

Cancer subdivided into more than 100 different diseases that characterized by uncontrolled cellular growth, local tissue invasion, and distant metastases.⁽¹⁾ Leukemia is a malignant hematopoietic disease characterized by an uncontrolled proliferation and block in differentiation of hematopoietic cells.⁽²⁾ These cells can spread to the lymph nodes, spleen, liver and other tissues. Leukemia broadly classified as acute or chronic referring to the cell affected and by the rate of cell growth and of myeloid or lymphoid according to the cell that is multiplying abnormally.⁽³⁾

 

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid disorders that result from a monoclonal proliferation and expansion of immature B or T lymphocyte progenitor in the bone marrow, blood, and other organs.^(4,5) Proliferation and accumulation of leukemic cells result in the suppression of normal hematopoiesis and involves various extramedullary sites especially liver, spleen, lymph nodes, thymus, central nervous system, and gonads. Acute lymphoblastic leukemia common in children but can occur in any age group. The healing rate of childhood acute lymphoblastic leukemia of more than 80% and the development of the treatment for this disease is one of the successes in the history of modern medicine.⁽⁵⁾ Acute lymphoblastic leukemia mostly occurred in children, with an incidence of 3 to 4/100,000 persons 0 to 14 years of age and 1/100,000 in patients older than 15 years in the United States. In children, Acute lymphoblastic leukemia represents 75% of all acute leukemia cases (which in turn represents 34% of all cancers in this age group), with an incidence peak at two to five years of age.⁽⁶⁾ The male slightly high affected in all age groups and a significant incidence among white children.⁽⁷⁾ Varieties of genetic and environmental factors related to ALL, it occurs mostly in patients with Down syndrome, Bloom syndrome, neurofibromatosis type I and ataxia-telangiectasia. Exposure in utero to ionizing radiation, pesticides, and solvents has also related to an increased risk for childhood leukemia.⁽⁷⁾ The signs and symptoms of ALL are sudden. Patients are suffering from a short history of fatigue or bleeding, malaise, lethargy, weight loss, fevers, and night sweats, patients with ALL suffering from one or more bone and joint pain, also present with asymmetric arthritis, low back pain, diffuse osteopenia, or lytic bone lesions.⁽⁸⁾

 

Anemia, abnormal leukocyte and differential counts, and thrombocytopenia are usually present at diagnosis, reflecting the degree to which bone marrow replaced with leukemic lymphoblast.⁽⁹⁾

The selection of treatment of ALL based on the clinical risk of relapse in the patient differs among subtypes of the disease. Three expected factors are essential in chemotherapy treatment which are; the age of the patient at a time of diagnosis, leukocyte count and the speed of response to treatment.⁽¹⁰⁾

 

Acute lymphoblastic leukemia patients require long time continuation therapy to reduce the duration of moderately intensive chemotherapy to 12 to 18 months or less have given poor results in both children and adults. Thus, patients treated for two years or more. A combination of methotrexate administered weekly and 6-mercaptopurine given daily constitutes the basis of most continuation regimens.⁽¹¹⁾ Using intermittent pulses of vincristine and a glucocorticoid (prednisone) or dexamethasone to the methotrexate/6-mercaptopurine combination is beneficial.⁽¹²⁾

 

Once a complete hematologic remission obtained, maintenance therapy started, maintenance doses will vary from patient to patient. The usual daily maintenance dose of 6-mercaptopurine is 1.5 to 2.5mg/kg/day as a single dose or (75mg/m²).⁽¹³⁾

 

The most frequent adverse reaction to 6-mercaptopurine is myelosuppression. The induction of complete remission of acute lymphatic leukemia frequently is associated with marrow hypoplasia.⁽¹⁴⁾ Six-mercaptopurine-induced hepatotoxicity is most common when doses exceed 2.5mg/kg/day.⁽¹⁵⁾ Rapid onset of jaundice, cholestasis, ascites, hepatic encephalopathy and elevated liver enzymes often associated with hepatic necrosis and severe fibrosis, can occur⁽¹⁶⁾.

 

Hyperuricemia and hyperuricosuria may occur in patients receiving 6-mercaptopurine because of rapid cell lysis accompanying the antineoplastic effect. Renal adverse effects minimized by increased hydration, urine alkalization, and the prophylactic administration of a xanthine oxidase inhibitor such as allopurinol. The dosage of 6-mercaptopurine should be reduced to one-third to one-quarter of the usual dose if treated with allopurinol concurrently.⁽¹⁵⁾

 

Nausea, vomiting, stomatitis, and anorexia are uncommon during initial administration but may increase with continued administration. Mild diarrhea and sprue-like symptoms noted occasionally, but it is difficult at present to attribute these to the medication.⁽¹⁵⁾ Six-mercaptopurine suppress cellular hypersensitivities and lower allograft repudiation. Inducement of immune reaction to infections and vaccines become subnormal in these patients; the antigen dose and a transitory relation to 6-MP will determine the grade of immunosuppression. This immunosuppressive effect carefully considered about infections and risk of subsequent neoplasia.⁽¹⁷⁾ Other adverse effects of 6-MP include hypersensitivity (2-3%), fever (1-10%), alopecia (<1%), hyperpigmentation (1-10%), rash (1-10%), secondary malignancy leukemia and myelodysplasia), cysts and polyps (2-6%), increased risk of abortion if taken in first trimester of pregnancy (category D) and oligospermia.⁽¹⁸⁾

 

SUBJECT, MATERIAL AND METHODS:

Study design:

A quasi-experimental study carried out at Medical City in Baghdad Teaching Hospital and a central teaching hospital of pediatrics under the supervision of consultant hematologist from December 2017 until June 2018. Sixty ALL patients and sixty healthy subjects selected to participate in this study. All patients complete the courses of the study successfully.

 

Patients Group:

Includes 60 patients with acute lymphoblastic leukemia on maintenance (continuation) phase receiving 6-mercaptopurine at least for two-month duration on daily doses based on body surface area. The total number of patients was 60 (40 male and 20 Female), among them, 44 were less than 18 years old (mean ± SD was 9.348 ± 5.131), and 16 were more than 18 years old (mean ± SD was 29.058 ± 7.9173).

 

Control Group:

Includes 60 healthy subjects' adults and children without any medical illnesses. PCR analysis made to thirty healthy subjects of them to compare thiopurine methyltransferase (TPMT) enzyme genes with patients, liver function, renal function, random blood sugar and complete blood count made to all sixty healthy persons to compare it with patients.  Of this group there were (40 male and 20 Female), among them, 42 were less than 18 years old (mean ± SD was 8.926 ± 5.326), and 18 were more than 18 years old (mean ± SD was 28.645 ± 7.482).

 

Data Collection:

Patients characteristics (such as age, weight, gender, B.S.A, date of the beginning maintenance phase, date of blood sampling, adverse effects of 6-mp and presence of other diseases obtained through patient interview. Plasma concentration of 6-mercaptopurine and 6-thioguanine in RBC measured by HPLC-UV. Genetic polymorphism of TPMT detected by polymerase chain reaction conventional (allele-specific method).

 

Complete blood count (Hb, W.B.C count, R.B.C count, platelets count, absolute neutrophils count), liver function tests (AST, ALT, ALP and total serum bilirubin T.S.B), renal function tests (serum creatinine and blood urea) and blood sugar concentration obtained at the same day of blood sampling.

 

Patient information sheet, including all the details that recorded for each patient who was acute ALL on maintenance phase.

Sample Collection and Preparation:

Ten milliliters of a venous blood sample drawn from each patient in the morning at 8:30AM – 11:30AM. These samples drawn from patients taking 6-MP at night on continues daily doses at least two consecutive months from the beginning of the maintenance phase. Five milliliters of blood sample divided into two EDTA containing a tube, in first tube 2ml put and stored in deep freeze at (–40 C^o) until time for genomic DNA analysis. In the second tube 3ml used to measure complete blood count (CBC) and the residue kept in 4-8C^o until total sample collection in the same day, then centrifuged for 5–10 minutes at 4000rpm to obtain and collect plasma in another tube for measuring 6-MP plasma concentration. The remaining RBC in the EDTA containing tube washed with sodium chloride 0.9% (normal saline) three times for each sample. Then a suspension of RBC was prepared and stored in deep freeze at (–40C^o) until time for 6-thioguanine-concentration measurement. The other 5ml used to measure AST, ALT, ALP, B. urea, S. creatinine, T.S.B and R.B.S. CBC calculated in hematology department, the others were done in educational laboratories (Baghdad Medical City). In addition to the above, 10ml of blood collected from 30 healthy control subjects to study genetic polymorphism of TPMT and to measure AST, ALT, ALP, B. urea, S. creatinine, T.S.B, R.B.S, and CBC compare it with ALL patients.

 

Statistical analysis of data:

Statistical analysis of the results obtained in this study included; mean±standard deviation (SD), analysis of variance (ANOVA) single factor, and correlation coefficient (r). The results of the analysis with P value < 0.05 were considered significant. Statistical analysis and graphs were carried out by Microsoft Office Excel 2007 software.     

 

RESULTS:

Table 1 shows the distribution of the age within study group and Fig.1 shows the distribution of the study population by gender.

 

Table 1: The distribution of the age within study group.

 

        

Fig. 1: The distribution of the study population by gender.

 

Adverse effects reported in the patients using ALL protocol:

Fig 2 shows the main adverse effect of the protocol was seen with higher incidence of jaundice, fever, decreased appetite, unusual tiredness or weakness, headache, stomach pain, dark urine and pale skin. Whereas, the fewer incidences among the common adverse effect are hemoptysis, painful or difficult urination, diarrhea, nausea and vomiting, chest pain and sore throat.

 

Renal function test (serum creatinine and BUN):

Table 2 points out that the mean serum creatinine increased significantly in patients ≤ 18 year (mean ± SD 0.97 ± 0.13) and > 18 year (mean ± SD 0.98 ± 0.12) compared to the control subjects (0.64 ± 0.19 and 0.64 ± 0.22) consequently. Similar trends were found for BUN in patients ≤ 18 year (mean ± SD 24.44 ± 6.92) and > 18 year (mean ± SD 27.33 ± 9.53) compared to the control subjects (14.87 ± 3.64 and 15.21 ± 0.22) consequently. Although these result were within the normal range value.

 

Liver function tests for the patients using 6-MP versus control subjects:

Table 3 denotes that the mean serum ALT increased significantly in the patients compared to the control subjects (60.66 ±14.26 vs. 31.52 ± 5.51). Similar trend were found for AST (45.71 ± 23.04 vs. 11.48 ± 7.05), ALP (99.63 ± 38.21 vs. 60.61 ± 19.52) and T.S. bilirubin (1.61 ± 0.58 vs. 0.40 ± 0.14 mg/dl).

 

Fig. 2: Percentage of reported adverse effects in the patients using ALL protocol

 

 

Table 2: Serum creatinine and BUN for the patients versus the control subjects using 6-MP.

 

Table 3: Serum ALT, AST and ALP in the control subjects versus the patients using 6- MP.

*Significant difference

 

Table 4: Random blood sugar (RBS) for the control subjects versus the patients using 6-MP.

*Significant difference

 

 

Table 5: Hematological feature of control versus patients using 6-MP

Hematological parameters (Normal range)	Group	Mean ± SD	P-value
RBC count (4.32-5.72)	Patients	3.68 ± 0.66	0.0004*
	Control	4.37 ± 0.94
WBC count (3.5-10.5)	Patient	3.48 ± 1.62	0.00008*
	Control	7.26 ± 1.70
Absolute neutrophil count//μm3 (2.5-7)	Patient	1.36 ± 1.12	0.0004*
	Control	4.43 ± 1.27
Absolute lymphocyte count//μm3 (0.9-2.9)	Patient	0.8100 ± 0.37	0.00752*
	Control	2.1800 ± 0.64
Platelets counts (150-400)	Patient	213.81 ± 83.78	0.00005*
	Control	344.07 ± 46.34
Hb mg/dl (12-17)	Patient	11.430 ± 1.51	0.00001*
	Control	14.550 ± 1.17

*Significant difference

 

Random blood sugar (RBS) for the control subjects versus the patients using 6- MP:

Table 4 shows that the mean RBS increased significantly in the patients compared to the control subjects (166.93 ± 87.56 vs.104.45 ± 16.74).

 

Hematological feature of control versus patients using 6-MP

Table 5denotes that the mean RBC count decreased significantly in the patients compared to the control subjects (3.68 ±0.66 vs. 4.37 ± 0.94). Similar trend were found for WBC count (3.48 ± 1.62 vs. 7.26 ± 1.70).

 

DISCUSSION:

Background:

Cancer incidence and mortality, in general, increase with age through much of adulthood, but earlier work has found that these rates decline among the elderly and adults. Leukemia is widespread cancer among children around the word. Acute lymphoblastic leukemia (ALL) participates to 76% of all leukemia cases, and 43% of all dooms of pediatric leukemia patients in the United States.⁽¹⁹⁾

 

General characteristic of the study population:

In this study, our patients were higher in children and young study population less than 18 years old (73.33%). The mean of the ALL patients less than 18 years old was 9.348 ± 5.131 years, and for those, more than 18 years old was 29.058 ± 7.9173 table (3-1). With a male: female 2:1.

 

The control subjects were selected randomly to reflect a reliable comparison with the patients. Sixty random volunteers were involved in this study. Sixty volunteers with gender-related to that of patients (40 male and 20 female). No significant difference in age of patients in comparison to the control subject, which excludes any effect of age on our study.

 

Genders:

Of greater significance, boys were noted to present with high-risk B-precursor ALL four times more than girls ⁽²⁰⁾. In this study, we record that the higher proportion of ALL found in male (66%), a significantly higher percentage of patients was male for both more and less than 18 years old.

 

Characteristics of the patients:

In this study, the mean period of using 6- MP was 13.94 months. All of the patients were in the maintenance stage of treatment to exclude the high dose used in induction stage. The dose of 6-MP for the patients in our study was within the precise dose/ m² of body surface area.

 

Adverse effects reported in the patients using ALL protocol:

In this study, in addition to the leukopenia, the adverse effect was recorded from the patients was jaundice, fever, decreased appetite, and weakness. The less commonly documented adverse effects of 6-MP have reported from our study was joint pain, heartburn, sores, and ulcer.

 

Next, to leukopenia, allergic reactions to 6-MP are the next prevalent, adverse effects. Whether nausea and malaise are also on an allergic basis has not been clear. Allergic reactions, fever, skin rash, joint pains, and back pain were the most common adverse effects⁽²¹⁾. Leukopenia was the most common adverse effect of AZA/6-MP treatment. Leukopenia and nausea/vomiting progressed in the early period of treatment of AZA/6-MP in patients with IBD⁽²²⁾.

 

Clinical laboratory tests for the patients versus the control subjects using 6-MP:

In this study, creatinine in serum and blood urea nitrogen was significantly elevated in patients compared to the control; in spite of it still at normal range, in patients ≤ 18 years (mean ± SD 0.97 ± 0.13) and > 18 years (mean ± SD 0.98 ± 0.12) when compared to the control subjects (0.64 ± 0.19 and 0.64 ± 0.22). Similar trends found for the blood urea nitrogen in patients ≤ 18 years (mean ± SD 24.44 ± 6.92), and > 18 years (mean ± SD 27.33 ± 9.53) compared to the control subjects (14.87 ± 3.64 and 15.21 ± 0.22) consequently. Which could a result of the kidney toxicity of 6-MP.

 

In acute leukemia, renal complications occur due to several factors including leukemic infiltration of the kidneys, therapy-related side effects such as tumor lysis syndrome, nephrotoxic drugs, and septicemias. Renal involvement can present as renal enlargement due to leukemic infiltrates or as a renal failure due to uric acid nephropathy. However, other causes such as nephrotoxic drugs, infections, and obstructive uropathy due to Para-aortic lymph nodes, retroperitoneal mass, urolithiasis, or ureteral clots can also occur⁽²³⁾.

 

No significant differences in serum urea and creatinine levels in patients treated with the chemotherapeutic agents. There is mild increase after chemotherapy but not significant; this indicates that chemotherapy is not directly toxic to renal tubules⁽⁶⁾.

 

In this study, a significant increase in serum creatinine and serum BUN were seen in both child and adult when compared with relative age with control subject, but they are still within normal range. In spite of weakly glomerular filtration rate (GFR) causing a condition of decreased urinary elimination, leads to retention and congregation of several nitrogenous waste products in the plasma and the body fluids, a variety in mean values of normal S. Cr level when evaluated in another age groups separately and also between males and females of various age groups⁽²⁴⁾.

 

Despite the common problem of hepatotoxicity with thiopurine drugs, there is a lack of studies with a significant number of well-characterized patients with this type of liver injury. Most studies have been limited to the irritable bowel syndrome patient population and focused on asymptomatic elevations of serum aminotransferase levels as the only evidence of liver injury⁽²⁵⁾.

 

In another study, liver toxicity is caused by 6-MP uncommon in the adult patients mentioned in another study. Although hepatic lesion linked with the increased mean of 6-MMP concentration, the sensitivity, and specificity of 6-MMP for drug-induced liver toxicity was with little researches⁽²⁶⁾. 

 

In our study, highly significant elevations of liver enzymes (AST, ALT, and ALP) in the patients compared with a control indicate the hepatotoxicity of 6- MP.

 

It is interesting that 6-MP, when used to treat leukemia in children, has resulted in unexplained symptomatic hypoglycemia. This low glucose level occurred by the action of a small molecule known as NR4A3 (nuclear orphan receptors) agonist, can elevate glucose in insulin target cells, although this occurs via both NR4A3-dependent and -independent actions; the last one is linked to an increment in phospho-AS160. Development of modern treatments strategies for insulin resistance established depending on these results⁽²⁷⁾.

 

These findings were not matching with our result, in which, a significant elevation of RBS seen in the patients compared to the control subject, although, many research recognized pancreatitis effect caused by 6-MP. This need for more investigations to conclude the possible etiology of hyperglycemia whether it occurred as a result of the disease or drugs used like steroids.

 

CONCLUSIONS:

In this study childhood, survivors of leukemia face many chronic side effects that can greatly impact their disease prognosis. It’s currently an inevitable consequence of curative treatment received. There is an importance of long-term follow-up, especially for those diagnosed at a young age.

 

Of considerable importance male was noted to exist with high-risk Bprecursor of acute lymphoblastic leukemia four times greater than female, proposing the requirements for more research into possible reasons behind this phenomenon.

 

Renal involvement is not uncommon in ALL. Renal involvement can present as an elevation in renal function test (creatinine and BUN)

 

Leukemic blast cell infiltration may cause significant deterioration of kidney function and renal toxicity. However, other causes such as nephrotoxic drugs, infections, and obstructive uropathy due to Para-aortic lymph nodes, retroperitoneal mass, urolithiasis, or ureteral clots can also occur. Although hematological malignancies commonly involve the liver, they rarely cause clinically significant hepatic disease.

 

In acute leukemia involvement of the liver is generally detectable clinically by the presence of hepatomegaly and high liver function test.

 

Hepatic infiltrations as the prodromal manifestation of acute leukemia are exceptional and carry a poor prognosis with a great danger of rapidly fatal progression in spite of relevant chemotherapy.

 

Metabolic disorders are common in ALL. Insulin resistance is emerging as a concern for long-term ALL survivors, as is diabetes. Diabetes, hypertension and cardiovascular events must evaluate.

 

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Received on 21.02.2019           Modified on 10.04.2019

Accepted on 23.05.2019         © RJPT All right reserved