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%.