A 4-year-old boy presented with an intermittent fever for two weeks, cold symptoms, and loss of appetite. On physical examination, the child was found moderately dehydrated, tachycardic, and tachypneic and demonstrated a hepatosplenomegaly. His peripheral blood tests showed 10% myeloid blasts with WBC (16.2 x 109/L), severe anemia (Hb 2.8 g/dL), and thrombocytopenia (platelets 6 x 109/L), as well as a monocyte count of 4.61 x 109/l. A bone marrow aspiration was performed and revealed 10% of myeloid blast cells. The patient was started on an induction regimen with cytarabine and rasburicase. Less than 24 hours after initiation of therapy, he developed fever and progressive respiratory failure. A chest X-ray showed a bilateral pulmonary infiltration. In the context of suspected sepsis, the broad-spectrum antibiotic treatment was started. Echocardiography showed signs of severe pulmonary hypertension (PHT). Despite inotropic support, mechanical ventilation, and early antibiotics, the patient deteriorated and was referred to our tertiary pediatric intensive care unit.
At arrival, his general condition was critical with signs of multiorgan failure and severe lactic acidosis. The neurological status appeared to be normal. His acute respiratory distress syndrome necessitated high-pressure ventilation (Figure 1(a)). Despite optimized conventional therapy, he rapidly developed cardiogenic shock. A veno-arterial (VA) ECMO was initiated via neck vessel cannulation, and immediate improvement in oxygenation was achieved (Figure 1(b)). ECMO flow was stable between 1.2 - 1.7 L/min during the whole support period. ACT was kept at 180 seconds. No major bleeding complications occurred. Mechanical ventilation was continued, and PHT therapy was initiated with sodium nitroprusside and nitrous oxide. First improvements in ventilation were observed on day 12 on ECMO support. On day 18, VA ECMO could be converted to a veno-venous (VV) ECMO by using a dual lumen Avalon ELITE cannula (MAQUET Cardiopulmonary AG, Germany) (Figure 1(c)). After seven days of VV ECMO support, the patient was successfully weaned on day 25 (Figure 1(d)). The neurologic assessment of the patient was limited during ECMO support due to pharmacological sedation. Following further hemodynamic improvement and weaning of sedation, the patient demonstrated a quadriplegia, global aphasia, and conjugate eye deviation. Subsequent MRI diagnostic revealed a central pontine myelinolysis. Certainly, it was caused by dyselectrolaemia with severe hypernatremia. Despite severe neurological impairment, his respiratory condition improved further, and 2 days later (day 30), he was extubated (Figure 2). Following extubation, a bilateral vocal cord paralysis of probably central origin was noticed.
Given the fast improvement of the patient, the initially paused chemotherapy with cytarabine was restarted early, thus allowing a cytogenetic remission on day 21 of ECMO support.
On day 34 of hospitalization, the patient was referred for evaluation for allogeneic hematopoietic stem cell transplantation to the transplantation center. A genetic testing revealed a KRAS and SETBP1 mutation. Given the severe neurological impairment, the decision was taken to proceed with bridging chemotherapy until improvement of the neurological status could be observed.
Five weeks later, the patient's clinical condition was normal with a remarkably improved neurological status and normalized vocal chord function. The patient could walk, even drive a 3-wheel bike, while his cognitive function was still impaired with a stammer requiring further speech and language therapy.
Six months later, he underwent allogeneic hematopoietic stem cell transplantation with a 10/10 HLA-matched unrelated donor donating bone marrow. The conditioning comprised fludarabine, targeted busulfan, and melphalan including rabbit ATG. He engrafted at day +26 and +23 with neutrophils and platelets of donor origin. The child was discharged home with minor cognitive impairment.