Result
A total of 120 pediatric ALL/LBL patients were treated in our Pediatric
Hematology Oncology and BMT Unit between 1st May 2016
and 31st March 2021. Chest X-ray was routinely
performed in all patients diagnosed with ALL/LBL, however CT chest could
be done in only 3 patients. Of these, 23 patients (19%) had
T-ALL/T-LBL. Eleven (48%) amongst these T-ALL/T-LBL presented with
SVCS. Routine chest X-ray helped us diagnose an additional of 6 patients
with radiological evidence of mediastinal mass, but had no clinical
symptoms of SVCS. All patients were males aged 4-16 years with a median
age of 9 years. Six patients (54%) were diagnosed as T-ALL, while the
remaining 5(46%) as T-LBL. Demographic details and clinical
presentations of these patients are described in Table 1.
The time from onset of symptoms to diagnosis ranged from 1 to 12 weeks
(median 3 weeks). Cough and dyspnea as predominant presenting symptoms
were seen in all the patients. Examination findings were suggestive of
decreased air entry in 5/11 patients (46%), muffled heart sounds in
4/11(36%), and distended neck veins in 4/11 patients (36%). Rarer
findings included sternal bulge, facial nerve palsy, pedal oedema and
cardiogenic shock in one patient each. Chest X-ray was the
1st radiological imaging done in all patients.
Mediastinal widening was seen in all (100%), and pleural effusion was
seen in 5/11 patients (45%). All underwent 2D- echocardiography, and
pericardial effusion, and cardiac tamponade was noted in 2(18%) and
4(36%) patients respectively. Two (18%) patients had hyperleukocytosis
on hemogram. One patient with facial nerve palsy, had negative malignant
cytology on CSF and no evidence of CNS disease on MRI brain hence
symptoms were thus attributed to SVCS. Central nervous system (CNS)
disease was seen in only 1 patient.
Prompt diagnosis of ALL/LBL could be reached in 10 patients (90%) by
Flow cytometry. Among these 10 patients, flow cytometric identification
of blasts was made in a peripheral blood sample in 3 patients (27%),
pleural fluid in 4(36%), pericardial fluid in 2(18%) patients, and
bone marrow aspirate sample in 1 patient (9%). Bone marrow aspiration
and biopsy was done under local anesthesia in sitting position. In one
patient diagnosis could not be reached by any method so treatment was
started empirically. CT guided biopsy of the mediastinal mass was
performed 24-hours after starting steroids and stabilization the
patient. Bone marrow examination was performed in the remaining patients
once they were stable after initiation of steroids. Diagnosis was
changed from lymphoma to leukemia in 2 patients. Initially, both were
diagnosed as lymphoma due to presence of blasts in pleural fluid but
later found to have blasts in bone marrow when tested.
Flow cytometry was performed on peripheral blood when circulating blasts
were present. As therapeutic and diagnostic measures when indicated,
patients underwent intercostal drain placement with continuous drainage
for pleural effusion and pigtail catheter drainage was done for
pericardial effusion. In view of difficulty and risk of sedation while
performing procedures like bone marrow examination or tru-cut biopsy,
such procedures were deferred where possible. Diagnosis was attempted by
doing flow cytometry on peripheral blood, pericardial/ pleural fluid.
All were started on corticosteroids soon after diagnosis of SVCS was
established at 60mg/m2/day of oral prednisolone or
equivalent dose of intravenous methylprednisolone or hydrocortisone
infusion.
Eight of eleven patients (72%) required pediatric intensive care unit
(PICU) admission ranging from 2 to 13 days (median- 4.5 days). Invasive
procedures such as pleurocentesis and Pig-tail catheter
pericardiocentesis were done in 4/11(36%) patients each. Oxygen
supplementation with nasal prongs was required in 9/11 (81%) patients,
and endotracheal intubation was required in 2 (18%) patients. Patients
with only radiological evidence of mediastinal mass without SVCS fared
better than this cohort in the induction period (need for intensive care
support 0% vs 72%).
Initial response to treatment was judged by relief of symptoms. Time to
onset of clinical response ranged from 1-13 days, with a median of 4
days. The radiological response was judged by the time to a significant
decrease of the original mediastinal widening on Chest X-ray, which
ranged from 4-20 days with a median of 7 days.
Two patients had thrombosis of bilateral brachial and subclavian veins
with extensive collaterals diagnosed by ultrasound Doppler of upper
limbs and were treated with low molecular weight heparin. Other known
complications of SVCS such as stroke, pulmonary embolism, and recurrent
laryngeal nerve palsy were not seen in any of our patients. None of our
patients needed any form of surgical intervention such as stenting or
thrombolysis.
All our patients were risk stratified and treated as per BMF-95
back-bone protocol. One patient abandoned treatment immediately after
initial stabilization and has been excluded from further analysis. Three
patients were stratified as high risk and 7 as medium risk as per BFM-95
stratification. The two patients with extensive venous thrombosis
received etoposide in place of the last 2 doses of L-asparaginase, and
another 1 was switched to BFM-95 High-Risk block in view of persistent
metabolically active residual disease on PET-CT scan. Hematopoietic stem
cell transplantation (HSCT) was offered to 2 patients. Both abandoned
treatment before reaching HSCT.
In our cohort of 11 patients, 3 abandoned treatment at various times
points. The follow-up and outcome
of this cohort is depicted in figure 1. Six out of the remaining 8 are
alive and in remission at last follow up. One patient died of
progressive disease and another one died of treatment related
complication. At a median follow up of 23-months (range 6-63 months)
overall survival and event-free survival was 75%. However, if include
the 3 children who abandoned therapy as events then event free survival
drops to just 55%.