Results
One-hundred ninety-nine children undergoing ALL maintenance therapy
having baseline characteristics as described in Table 1 were recruited.
Median age was 72 months (range – 19-186 months). Male: female ratio
was 1.28:1, 55.3% children (n=110) were HR and 44.7% (n=89) children
were SR. Ninety-four (47.2%) children received CRT, of which 93
received prophylactic 12 Gy CRT and one child received 18 Gy of CRT due
to initial CNS positive status.
Ninety-one (45.7%) children developed a total of 147 episodes of severe
infections during maintenance chemotherapy. Respiratory system was the
most common site affected (59.3% of children and 55.8%. of episodes
with severe infection) (Table 2). Gastrointestinal and central nervous
system were the most common non-respiratory systems involved. Febrile
neutropenia without any evident focus of infection was second most
common presentation (24.1% of children with severe infection and 19%
of total episodes of severe infection). Leucopenia
(TLC<1000/cumm) was present in 40 episodes (27.2%) and in 35
children (38.5%) with severe infection. Five children required inotrope
support while intensive care unit (ICU) admission for ventilator support
was needed for 4 children. Three (3.3% of children with severe
infection) children succumbed to death during severe infection and two
of these deaths were due to respiratory infections. Eight children
(8.7%) had culture positive infections, Escherichia Coli and
Pseudomonas Aeruginosa being the common organisms. Severe infections
were high during the initial months of maintenance phase chemotherapy
compared to the later months (Figure 1). This may be due to the more
severe immunosuppression resulting from the intensive reinduction and
reconsolidation chemotherapy phases preceding the maintenance phase.
Out of the total 91 children, who developed severe infections, 42
children were ≤5 years and 49 children were >5 years of
age. Proportion of children with severe infection and with respiratory
infection was significantly more in ≤5 years age group compared to the
older children (P=0.034, 0.015, respectively), while proportion of
children who developed severe infection involving systems other than
respiratory system was similar in both age groups (P=0.881) (Table 3).
Female children developed significantly more severe infections and also
respiratory infections during maintenance phase (P=0.008 and 0.046,
respectively) (Table 3). In both SR and HR groups, proportion of
children with severe infections, respiratory infections, non-respiratory
infection, ICU admission and inotrope requirement were similar (P=0.071,
0.288, 0.066, 0.327, 0.249) (Table 3).
Serum immunoglobulin estimation during maintenance phase revealed
hypo-IgM in 172 (86.4%) children and hypo-Ig G in113 (56.8%). (Table
1) In the 6-10 years age group (n=87), 24 (27.6%) children had IgA
levels <40 mg/dL and 63 (72.4%) children had normal IgA
levels (>40 mg/dL). We could not precisely assess the exact
number of children with hypo-IgA in this age group as the cut off for
hypo-IgA in this age group was 33 mg/dL, while the lower limit of kit
for IgA levels was 40 mg/dL. Among the rest of children (n=112), 80.4%
(90) had hypo-IgA and 19.6% (22) had normal IgA levels. One-hundred
eighty (90.5%) children had decreased levels of at-least one
immunoglobulin class, while 64 (32.1%) children had decreased levels of
all three immunoglobulin classes. Proportion of children with hypo-IgG,
hypo-IgA hypo-IgM, hypoglobulinaemia of at-least one immunoglobulin
class and hypoglobulinaemia of all immunoglobulin classes was
significantly high in ≤5 years age group as compared to >5
years age group (P=0.044, <0.001, 0.024, 0.009,
<0.001, respectively). For children with hypo-IgA, the
difference remained significant even after excluding 6-10 years age
group children. (Table 1)
Percentage of children developing severe infections as well as
respiratory infections was significantly higher among patients with
normal IgG levels compared to those with low IgG levels (P=0.045 and
0.022, respectively) (Table 4). Similarly, non-respiratory infections
was significantly higher in a group of children who did not have low
levels of any of the immunoglobulin class compared to children who had
hypoglobulinaemia of at-least one immunoglobulin class (P=0.039,
respectively) (Table 4).
On univariate analysis for factors influencing the occurrence of severe
infection during ALL maintenance phase, younger age at the time of
recruitment, female gender, age group ≤5 years and normal IgG levels
were significantly associated with increased risk of severe infection.
Odds ratio (OR) (95% CI) was 0.991 (0.984 – 0.99; P=0.024) for
children with older age (in months) at the time of recruitment, 0.587
(0.329 – 1.046; P=0.070) for children in age group >5
years, 2.199 (1.239 – 3.903; P=0.007) for female gender and 0.565
(0.319 – 0.998) (P=0.049) for hypo-IgG. On multivariate analysis, only
female gender had significantly increased risk of severe infection
[OR. (95% CI) 1.970 (1.088 – 3.566) (P=0.025)] (Table 5).