this retrospective , hospital - based , observational study was carried out from august 2014 to july 2015 after obtaining necessary permission from the institutional ethics committee . diagnosed all patients admitted to the department of clinical haematology of scb medical college during the study period being treated with l - asp - based chemotherapy ( mcp 841 protocol )
all newly diagnosed indoor patients on induction therapy with the mcp 841 protocol , of either gender and up to 40 years of age , were included in the analysis .
patients on any other drug other than those in the mcp 841 protocol that could have altered the blood glucose levels were excluded from the study .
patients having abnormal plasma glucose level before starting therapy with l - asp were also excluded from the study .
patients bed head tickets were collected from the record section of the hospital . under the mcp 841 protocol ,
a patient is on l - asp intramuscular every other day on days 220 of the first induction therapy .
time of onset of hypo / hyperglycemia , persistence of plasma glucose alteration , and patient outcome were noted .
fasting plasma glucose ( fpg ) levels were noted before the start of treatment with l - asp , on day 6 and day 12 of l - asp therapy and after the stoppage of l - asp therapy .
differences in adr characteristics of native and pegylated l - asp were also noted and compared .
the serum amylase levels of all these patients were estimated to exclude the possible pancreatitis . paired sample t - test
was applied using medcalc version 12 -  1993 - 2013 medcalc software bvba ( acacialaan 22,8400 ostend , belgium ) to compare the fpg of patients before treatment with l - asp and on day 6 of l - asp treatment .
paired sample t - test was applied using medcalc version 12 -  1993 - 2013 medcalc software bvba ( acacialaan 22,8400 ostend , belgium ) to compare the fpg of patients before treatment with l - asp and on day 6 of l - asp treatment .
out of the 146 cases included for analysis , 129 were on native l - asp and only 17 were on pegylated l - asp .
twenty - one percent of patients showed altered plasma glucose level out of 146 cases ( thirty in number ) .
a total of 17 patients developed hypoglycemia ( fpg < 65 mg / dl ) whereas only 13 patients developed hyperglycemia ( fpg > 100 mg / dl ) .
the serum amylase levels of all these patients were normal which showed the absence of pancreatitis .
the median age in the hypoglycemia group was 5.5 years which is much less than that in the hyperglycemia group ( 19.5 years ) .
the male : female ratio was 13:4 in hypoglycemia group and 10:3 in hyperglycemia group [ table 1 ] . demographic characteristics of patients on l - asparaginase of patients who were on native l - asp , 20.9% developed either hypo- or hyper - glycemia . on the contrary , in patients who were on pegylated l - asp
all of them had hyperglycemia ( fpg > 100 mg / dl ) [ figure 1 ] .
percentage of patients with plasma glucose alteration out of the total thirty patients who developed abnormality in fpg , 56.67% developed hypoglycemia whereas 43.33% had hyperglycemia . in majority of the cases , the fpg abnormality developed after taking three doses of l - asp in a particular cycle of chemotherapy .
the number of patients who developed hypo- and hyper - glycemia after administration of native l - asp was 17 and 10 , respectively . on the contrary ,
all patients in hypoglycemic group had normal plasma glucose level before starting the treatment ( mean = 77.5 mg / dl ) .
most of them developed hypoglycemia ( mean = 60.6 mg / dl ) on day 6 which returned to normal ( mean = 67.3 ) after stoppage of l - asp treatment .
similarly , patients in hyperglycemia group had a mean plasma glucose of 86.5 mg / dl . on day 6 , majority of the patients
hyperglycemia persisted even after the stoppage of l - asp treatment ( mean = 121.6 mg / dl ) .
when the mean plasma glucose levels before the start of treatment with l - asp were compared with the values on day 6 by paired t - test , the p values for the hypo- and hyper - glycemia groups were found to be 0.0012 and 0.0309 , respectively .
l - asp , an enzyme , has a wide application in many therapeutic protocols , including all . during all treatment , glucose levels
are routinely monitored because many patients develop hyperglycemia , presumably because of glucocorticoids and l - asp .
unexpectedly , many of our patients experienced repeated fasting hypoglycemia during induction and maintenance therapy . since altered fpg level can change the clinical outcome of patients , it was thought imperative to probe the exact course of hypo / hyperglycemia so that appropriate measures can be taken .
most patients were given native l - asp and only a few were given pegylated l - asp , may be due to cost factor .
approximately , one - fifth of the patients on l - asp therapy developed abnormal plasma glucose levels .
most of the patients who developed hyperglycemia belonged to higher age group ( median age = 19.5 years ) compared to patients who have developed hypoglycemia ( median age = 5.5 years ) .
this may be due to the fact that , in patients with higher age group , pancreatic reserve is less compared to younger age group .
however , there is no significant difference between male to female ratio so far l - asp - induced abnormal plasma glucose levels ( hypo- or hyper - glycemia ) are concerned . in this study ,
as per the american diabetes association 2016 guidelines , fpg 100125 mg / dl is taken as impaired fasting glucose and > 126 is diabetic .
hypoglycemia is taken as < 65 mg / dl because research in healthy adults shows that mental efficiency declines slightly but measurably as blood glucose falls below 65 mg / dl .
fpg abnormality was observed in 20.9% of the cases in native l - asp group whereas only in 17.6% in pegylated l - asp group .
we could find only cases of hyperglycemia in pegylated l - asp group whereas incidences of both hypoglycemia and hyperglycemia were observed in native l - asp - treated group .
almost all the patients developed statistically significant abnormal glucose level after 3 dose of l - asp which may be due to the fact that the destruction of the endocrine pancreas is dose - dependent .
however , though hypoglycemia returned to normal level after the end of the chemotherapy cycle , hyperglycemia persisted for longer duration almost till the end of observation in our study in most patients . given the time relation between l - asp administration and abnormal plasma glucose levels , we presume that our patients experienced l - asp - induced hypoglycemia .
tanaka et al . in 2012 have reported that inappropriate insulin secretion , normal free fatty acids , and low ketone bodies during severe hypoglycemia indicate hyperinsulinism , suggesting that l - asp - induced hypoglycemia is a result of insulin hypersecretion .
there were no other drugs that could have potentially induced hypoglycemia during the study period .
glucocorticoids are known to induce hyperglycemia through insulin resistance and gluconeogenesis during induction therapy for childhood all .
we suspect that parallel use of glucocorticoids may mask the hypoglycemic effect of l - asp .
misgar et al . in 2014 have reported a case of 15-year - old boy who developed l - asp - induced hypoglycemia .
use of l - asp has recently become even more common in the adult all regimens .
we believe that in addition to the effect of l - asp on leukemic cells , it is important to pay more attention to its pharmacological features and physiological mechanisms .
greater knowledge of these effects will enable clinicians to understand and develop appropriate strategies for l - asp use in chemotherapy regimens .
hsu et al . in 2002 reported one case of diabetic ketoacidosis and persistent hyperglycemia as long - term complications of l - asp - induced pancreatitis .
mondal et al . in 2010 reported two cases of diabetic ketoacidosis with l - asp therapy .
quintanilla - flores et al . in 2014 reported one case of acute pancreatitis and diabetic ketoacidosis following l - asp / prednisone therapy in all .
hence , to the best of our knowledge , there are only two reported cases of hypoglycemia induced by l - asp therapy by tanaka et al . of tokyo , japan , and misgar et al . of kashmir ,
however , in this retrospective study of ours , we have got 17 hypoglycemia as well as 13 hyperglycemia cases indicating the adverse effects of l - asp .
our study reveals that a significant percentage of cases ( 21% ) have developed abnormal plasma glucose level among the study population .
most of them developed hypoglycemia and they were in lower age group , whereas the higher age group patients developed hyperglycemia . in comparison to peg l - asp , native one was associated with more incidences of abnormal fpg . in majority of the cases , the fpg abnormality developed after taking three doses of l - asp in induction phase of mcp 841 protocol .
identification of hypoglycemia as an adverse effect will enable clinicians to understand and develop appropriate strategies for l - asp use in chemotherapy regimens .
in addition to the effect of l - asp on leukemic cells , it is important to pay more attention to its pharmacological features and physiological mechanisms .
 objectives : the objective of this study was to evaluate any abnormal change in plasma glucose levels in patients treated with l - asparaginase ( l - asp)-based chemotherapy regimen in patients of acute lymphoblastic leukemia ( all).materials and methods : this retrospective , hospital - based study was conducted in patients of all , admitted to the clinical haematology department of a tertiary care hospital of odisha from august 2014 to july 2015 . 
 indoor records of 146 patients on multi - centered protocol-841 were evaluated for any alteration in plasma glucose level , time of onset of hypo / hyperglycemia , and persistence of plasma glucose alteration.results:twenty-one percent of patients showed abnormal plasma glucose level . 
 most of these patients developed hypoglycemia and were of lower age group . 
 most of these patients developed hypoglycemia and were of lower age group , whereas a majority of higher age group patients developed hyperglycemia . 
 in majority of the cases , abnormal glucose developed after three doses of l - asp . 
 hypoglycemia subsided whereas hyperglycemia persisted till the end of our observation period.conclusions:l-asp produces more incidences of hypoglycemia than hyperglycemia in a good number of all patients towards which clinicians should be more vigilant 
 . however , hyperglycemia persists for a longer duration than hypoglycemia . 
Materials and Methods
Statistical Analysis
Results
Discussion
Conclusions
Financial Support and Sponsorship
Conflicts of Interest