Cancer does not wait: Safeguarding care for pediatric acute lymphoblastic leukemia patients during the COVID‐19 pandemic in a Mexican hospital

Abstract

access to quality care for children with leukemia before the COVID-19 pandemic was already disadvantaged, with 5-year survival rates of 40%-60% compared to 90%-95% in developed countries. 1,2 Thus, safeguarding care of acute lymphoblastic leukemia (ALL) patients during the COVID-19 pandemic has represented a challenge.We analyzed 553 visits from 89 patients with ALL in "Hospital Universitario Dr. José Eleuterio Gonzalez." We conventionally administer all chemotherapy in an outpatient backbone. Some of the strategies implemented were increasing the capacity of infusion beds, offering telemedicine follow-up 24/7, continuing with the transplant program with outpatient intent, providing social support, and partnering with non-governmental organizations to assist families in paying for chemotherapy when needed. In our center, we did not modify or reduced intensity of the chemotherapy regimen. In addition, SARS-Cov-2-positive patients in induction received Capizzi chemotherapy regimen.Chemotherapy administration was timely and performed as per the protocol in 83% (n = 459) of the records reviewed. However, adherence was lower during the consolidation and intermediate maintenance phases (60.9% and 64%) and was associated with a shortage of cytarabine and methotrexate.The main causes of treatment delays were lack of financial resources (2.45), lack of inpatient beds (1.8%), and chemotherapy stock-outs (1.3%). In addition, the treatment abandonment rate was 3.3%.Other centers in low-and middle-income countries have reported their challenges during the pandemic, including missed or delayed diagnosis, chemotherapy shortages, shortfall of blood products, 3 and closure of HSCT programs. 2,4 Also, Gratz et al. reported decreased financial support, reduced clinical staff, and decreased available beds.The lack of availability of inpatient beds in our center was overcome by providing an ambulatory treatment regimen. If the treatment delay was >5 days, the 6-h outpatient infusion of methotrexate was implemented for low and intermediate risk. 5 During this time, 22 patients (24.7%) had a positive PCR test for SARS-CoV2; the median age was 5 years (range, 0.9-15). Two patients (9%) were diagnosed with COVID-19 and ALL simultaneously, eight patients (36%) during intensive phases of treatment, and ten (45%) with extended maintenance. In addition, two patients were diagnosed after haploidentical HSCT.The incidence of COVID-19 in our series was 24.7%, while other LA centers reported 13.1% and 58%. 6,7 Our mortality rate was 4.5%, similar to the global registry of Covid reported 8 ; however, another group in LA reported up to 37%. 6 Critical or severe illness was classified in 18%.Seven patients (32%) developed pneumonia, and two (9%) had multisystem inflammatory syndrome. Five (22.7%) required oxygen support, and two (9%) required mechanical ventilation. Three patients (13.6%) currently have late sequelae.The additional support interventions in our center allowed the continuity of ALL treatment for >80%. However, our high rate of abando...

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).…”

“…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). Reported blood cancer status for the leukaemia in children infected with SARS-CoV-2 were active (n = 258/574, 44.9%) (8, 12-15, 17, 19-21, 23, 24, 29, 31, 32, 34, 35, 37, 40, 58-60, 64, 66, 73, 74, 76, 78, 79, 81, 82, 85, 86, 90, 92, 93, 95, 97-100, 102, 103, 108-112, 114, 115, 118, 120-122, 124, 127-129, 134, 136, 140, 142, 143, 146, 148-151, 154, 156, 158-160, 167, 169, 170, 172, 174, 175, 177), remission (n = 256/574, 44.6%) (3, 4, 8, 14, 15, 21, 23-28, 30, 33, 35-37, 40, 59-62, 67-72, 74, 78, 84, 89, 91, 92, 94, 107, 126, 128, 132, 135, 137, 139, 141, 150, 155, 157, 163, 167-177), or relapsed/refractory (n = 60/574, 10.4%) (7,13,14,29,37,63,67,74,77,80,92,106,117,125,131,133,147,150,169,171,173,174,176,178), however, blood cancer status in these leukaemia cases was not reported in a high percentage of patients (n = 567/1141, 49.7%) (18,20,21,38,39,92,96,104,108,113,…”

“…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).…”

Treatment of Ph-Negative Acute Lymphoblastic Leukemia in Adolescents and Young Adults with an Affordable Outpatient Pediatric Regimen

“…On the contrary, our treatment abandonment rate in pediatric patients is 3%. 26 Prior and current healthcare reforms in Mexico continue to exclude patients with leukemia older than 18 years from universal coverage, which has been successfully established for children and adults with other cancers. 27 Considering that over 60% of the population earn less than $500 USD per month, 1/3 of each intensive treatment block cost, the abandonment rates are logical ( Table 4 ).…”

Securing access to a comprehensive diagnostic panel for children with suspected acute lymphoblastic leukemia: Results from the Mexico in Alliance with St. Jude “Bridge Project”

“…Despite the aforementioned changes in the Mexican health system and the COVID-19 pandemic, MAS has grown to engage over 70 healthcare institutions in Mexico in collaboration and quality improvement activities and over 25 in modernization and evidence activities (see Figure 1 ). MAS has documented health system challenges to improve outcomes for children with ALL ( 18 , 19 ), operationalized a model to increase access to specialized diagnostic testing for children with suspected ALL ( 20 ), developed and implemented an evidence-based consensus-derived ALL treatment guideline ( 21 ), expanded early detection of inpatient clinical deterioration utilizing pediatric early warning systems ( 22 ), improved time to antibiotic administration in patients with suspected febrile neutropenia ( 23 , 24 ), helped sustain treatment continuity during the COVID-19 pandemic ( 25 , 26 ), developed human resources for quality improvement and research ( 27 ), and nurtured collaboration with over 20 government agencies, professional organizations, and foundations ( 28 ).…”