Hematopoietic stem cell transplant in two pediatric patients testing positive for SARS‐CoV‐2: A case report

Abstract

Background The SARS‐CoV‐2 pandemic brought challenges to all areas of medicine. In pediatric bone marrow transplant (BMT), one of the biggest challenges was determining how and when to transplant patients infected with SARS‐CoV‐2 while mitigating the risks of COVID‐related complications. Methods Our joint adult and pediatric BMT program developed protocols for performing BMT during the pandemic, including guidelines for screening and isolation. For patients who tested positive for SARS‐CoV‐2, the general recommendation was to delay BMT for at least 14 days from the start of infection and until symptoms improved and the patient twice tested negative by polymerase chain reaction (PCR). However, delaying BMT in patients with malignancy increases the risk of relapse. Results We opted to transplant two SARS‐CoV‐2 persistently PCR positive patients with leukemia at high risk of relapse. One patient passed away early post‐BMT of a transplant‐related complication. The other patient is currently in remission and doing well. Conclusion These cases demonstrate that when the risk associated with delaying BMT is high, it may be reasonable to proceed to transplant in pediatric leukemia patients infected with SARS‐CoV‐2.

Blood cancer in children infected with COVID-19: A comprehensive systematic review

“…Clinical course of COVID-19 in blood cancer children was severe (n = 111, 8.6%) or critical (n = 47, 3.6%), and 41 children (3.2%) eventually died related to COVID-19. Indeed, majority of blood cancer children who died from SARS-CoV-2 infection had relapsed/refractory and advanced blood cancer (7,37,74,77,92,147,150,171,173,176,178) or signi cant medical comorbidities in addition to the uncontrollable cancer (17,19,21,65,99,104,108,110,138,150,153,170,172). Lower COVID-19 severity in blood cancer children infected with SARS-CoV-2 compared to the adults can be explained by the following theories: a) Less expression of angiotensin-converting enzyme 2 distribution that may limit SARS-CoV-2 entry into child's body organs and subsequent in ammation, hypoxia, and tissue injury (184), b) Less risk to hyper in ammatory immune response in children (185), and/or c) Immature receptor system, immune-system-speci c regulatory mechanisms, and possible cross-protection from other common pathogens in children (186).…”

“…Leukaemia was the rst most-common blood cancer in children who experienced COVID-19 (n = 1141, 88.5%) (3, 4, 7, 8, 12-15, 17-21, 23- 1). Among them, 579 have unclassi ed lymphoblastic leukaemia (50.7% of all leukaemias) (3, 4, 8, 12, 13, 15, 19-21, 23, 24, 26, 29-32, 39, 40, 61, 67, 70-72, 74, 75, 81, 82, 84, 86, 92, 104, 108, 113, 116, 123, 127, 132, 150, 153, 155, 161, 162, 167-174, 177, 178), 202 have unspeci ed leukaemia (17.7%) (14,18,20,35,93,96,103,107,134,147,159,167,176), 185 have B-cell lymphoblastic leukaemia (16.2%) (7, 13, 27, 28, 33, 34, 36-38, 58-60, 62, 63, 66, 68, 73, 78-80, 85, 89, 90, 94, 95, 97-100, 102, 109, 112, 115, 119-122, 124, 125, 128, 129, 131, 133, 135-137, 139, 140, 142, 143, 146, 151, 154, 156, 158, 163, 175), 150 have unclassi ed myeloid leukaemia (13.1%) (13, 15, 17, 19-21, 23, 25, 31, 32, 37-40, 59, 64, 67, 69, 77, 78, 91, 92, 94, 104, 106, 108, 110, 111, 113, 114, 116, 117, 123, 128, 129, 141, 148-150, 153, 160, 171-175), 23 have T-cell lymphoblastic leukaemia (2%) (37,38,59,76,78,118,119,126,128,157,175), and 2 have biphenotypic leukaemia (a mixture of both types of lymphoblastic and myeloid leukaemias) (0.2%) (23,99). Most of those patients had acute leukaemic conditions (n = 892, 78.2%) (3, 4, 7, 8, 13-15, 17, 19-21, 23-34, 36-40, 58-64, 66-82, 84-86, 89, 90, 92-95, 97-100, 102, 104, 106, 108-129, 131-133, 135-137, 139-143, 146-151, 153-158, 160-163, 167-175, 177, 178) and only few cases had chronic leukaemia (n = 5, 0.4%) (91,92,129).…”

“…Many of these leukaemic children infected with SARS-CoV-2 were found to have active concurrent infections (n = 96) [including unspeci ed pathogens (n = 35) (19 bacteria (14,37,108,151,(171)(172)(173), 12 fungi (66, 108, 172, 173), and 4 other unknown pathogens) (113); Rhinovirus (n = 6) (28, 76, 133, 153, 160); Pseudomonas (n = 6) (17,19,21,31,33,128); Aspergillus (n = 4) (61, 71,110,171); Dengue virus (n = 4) (169); In uenza A virus (n = 4) (72,133,146,168) (13,19,23,62,64,74,77,78,84,106,114,119,128,129,133,147,153,160,176,178) and autologous (n = 1) (27)], graft versus host disease (n = 15) (13,19,64,99,114,128,129,136,153,160,…”

“…Most common clinical symptoms from leukaemia were febrile neutropenia (n = 29) (21,25,31,58,59,61,66,76,84,97,111,122,136,139,148,149,173,175), sepsis (n = 23) (17,21,37,59,99,110,114,132,150,154,172,173), bone marrow suppression (n = 21) (3,25,28,59,60,81,82,86,90,95,112,114,122,125,133,134,149,151,169), multiorgan failure (n = 18) (17,37,59,99,…”

“…Paediatric leukaemic cases with concurrent COVID-19 had a documented mortality of 99 (8.7%) (7, 8, 15, 17-21, 35, 37-40, 59-61, 74, 77, 84, 92, 93, 99, 104, 108,110, 113, 116, 147, 150, 153, 161, 171-173, 175, 176, 178), while 1034 (90.6%) of the leukaemic children recovered(3, 4, 8, 12-15, 18-21, 23-40, 58-60, 62-64, 66-82, 84-86, 89-100, 102-104, 106-109, 111- 129, 131-137, 139-143, 146, 148-151, 153-163, 167-177). Mortality was COVID-19-related in a considerable number of paediatric leukaemic cases (41/99, 41.4%)(7,21,35,39,40, 61,74, 84,92,93,99,104,113,150,153, 161,171,173,175, 176), however, COVID-19 was not attributable to death in many of the reported leukaemic children (36/99, 36.4%) (8,15, 17, 19-21, 37, 39, 40, 59, 60, 77, 92, 104, 108, 110, 116, 154, 171, 173, 175) and few studies failed to report if COVID-19 was a leading or an underlying cause of death in those leukaemic children (22/, 22.2%)(18, 38,93,147,172, 178) (see Table2).LymphomaLymphoma was the second most-common blood cancer in children who experienced COVID-19 (n = 133, 10.3%)(12-22, 31, 35, 38-40, 57, 59, 67, 78, 87, 88, 92, 93, 96, 101, 105, 108, 123, 128-130, 144, 145, 150, 152, 164, 165, 169-175, 177, 178) (see Table1). Among them, 59 have non-Hodgkin's lymphoma (44.4% of all lymphomas)(12, 15, 16, 18, 20-22, 32, 38, 39, 57, 59, 67, 78, 87, 101, 105, 129, 130, 144, 150, 165, 169-171, 174, 175, 177), 38 have unspeci ed lymphoma (28.6%)(14,35,92,93, 96, 108,172,173, 178), and 36 have Hodgkin's lymphoma (27.1%)(13, 15, 17, 19-21, 38, 40, 67, 88, 123, 128, 145, 150, 152, 164, 169-171, 174, 177).…”