Dear Editor,
We would like to present a case emphasizing the careful patient selection and early initiation of ECMO in select patients leading to long-term successful outcomes.
An 18-year-old female in acute respiratory failure was mechanically ventilated and initiated on veno –venous ECMO given worsening breathlessness. Following clinical improvement, she was de-cannulated after 5 days and underwent tracheostomy requiring high flow oxygen. Broncho-alveolar lavage (BAL) fluid isolated acute myeloid leukaemia blasts, and bone marrow (BM) biopsy confirmed AML. Genetics confirmed KMT2A-rearranged AML. She underwent induction with Daunorubicin ,Cytarabine ( 3 + 7 regimen), and one dose of Gemtuzumab Ozagamycin. Tracheostomy was reversed on day 18 post-induction. The day 28 BM was in remission, but BAL fluid contained 30% blasts. She was re-induced with Fludarabine and Cytarabine, Filgrastim, Idarubicin (FLAG-IDA). BM post-FLAG-Ida revealed an MRD-negative marrow remission on flow (< 10 − 4) with 2% blasts in BAL fluid ,switched to FLAG-Ida with Venetoclax 100 mg [1], after which she achieved molecular remission in the marrow with no evidence of AML on BAL. Lung function tests showed a restrictive ventilatory defect and gas transfer defect was noted at the alveolar level (DLCO 67%; Kco 112%).Given the poor lung function, despite the myeloid sarcoma, total body irradiation-based conditioning was avoided but she was considered fit for a myeloablative haploidentical transplant with Thiotepa, Busulfan, and Fludarabine conditioning followed by Cyclosporine, Mycophenolate mofetil, and post-transplant Cyclophosphamide as immunosuppression. She developed grade 2 skin GVHD after stopping immunosuppression, requiring oral steroids. She is now one-year post-transplant, with bone marrow in molecular remission and full-donor chimerism. Lung function after one-year post-allograft showed FEV1 74%, DLCO 92%; Kco 113%.
Discussion
AML with myeloid sarcoma is often associated with a poor prognosis. [2] Many patients are deemed unfit for transplant because of poor organ function, performance status, and co-morbidities. Leukaemia-related lung injury can occur due to high blast counts causing poor tissue perfusion; pulmonary leukemic infiltration or acute lysis pneumopathy, a cell-mediated process post-chemotherapy [3]. To our knowledge, this is the first case of respiratory failure due to pulmonary myeloid sarcoma bridged with ECMO for initial management and subsequently salvaged with myeloablative haploidentical transplant.
Multicentre retrospective analysis in Europe shows that overall survival following veno-venous ECMO in HMs is poor; hence its role remains unclear [4]. Adverse risk factors identified were high lactates and progressive disease and overall survival at day 60 was about 25–30% in patients with HM. [4, 5] One study showed a benefit of ECMO in HM, with survival of 50% [6].
Veno-venous ECMO is an option in patients with HM presenting in ARF where mechanical ventilation is insufficient. ECMO in such cases could be used as a bridge to recovery by providing adequate ventilation and avoiding additional lung damage due to mechanical ventilation. Respiratory distress and ARF are the commonest indications for ICU admission in HM patients. Half of all patients admitted require invasive mechanical ventilation and the mortality is 55–70% [7] which is mainly due to co-occurrence of severe pulmonary dysfunction and nosocomial infections, in conjunction with underlying malignancy and bleeding risk secondary to thrombocytopenia, inability to initiate ECMO either due to scarce resources or comorbidities that deems them unfit for ECMO. [8]
With the advent of newer targeted chemotherapy, improvements in ventilation strategies for acute respiratory distress syndrome, newer anti-microbials, better ICU management of HM patients, and careful patient selection, ECMO can be used as an artificial lung in providing extracorporeal gas exchange and minimizing trauma to the lungs due to mechanical ventilation. [9]
CT chest axial lung window reconstruction image showing extensive centrilobular air space deposits
Conclusion
ECMO in HMs acts as a bridge to provide adequate ventilation, limiting lung damage due to high-pressure ventilation. It provides sufficient time for chemotherapy to eliminate leukemic cells reducing the disease burden.
Acknowledgements
None.
Authorship contributions
Concept and design: SP, CB, DIM. Contributed to the writing of the manuscript: SP, RD IS, CB, DIM. Critical editing: SP, CB, DIM. Final approval of manuscript: SP, RD, IS, CB, DIM.
Funding Statement
This study did not receive any specific fund from a government or private funding agencies.
Conflict-of-Interest Statement
None declared for all authors.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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