COVID-19 and Adult ALL: Frequently Asked Questions
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(Version 2.1; last updated January 22, 2021)
Input from Wendy Stock, MD; Anand A. Patel, MD; Kristen O’Dwyer, MD; Renato Bassan, MD; Xianfeng Zhou, MD; Xiao-jun Huang, MD, PhD; Mark Litzow, MD; Elias Jabbour; Dan DeAngelo, MD, PhD; Selina Luger, MD, FRCPC; Nicola Gokbuget, MD; Richard Larson, MD; and Jacob Rowe, MB, BS.
Note: Please review ASH's disclaimer regarding the use of the following information.
Are you changing your approach to initial induction and intensive post-remission therapy?
Testing for SARS-CoV-2 is recommended before initiating intensive chemotherapy for ALL, irrespective of symptoms. If patients are SARS-CoV-2 positive, delay systemic treatment although IT therapy may be given if CNS symptoms are present. If SARS-CoV-2 testing is not available, consider careful symptom screening and a chest CT scan instead. We would recommend resumption of treatment of ALL in patients who have had COVID infections approximately 14 days following resolution of symptoms. Patients may still have + COVID PCR tests for weeks after COVID infection (possibly due to detection of viral fragments that have not cleared) but limited patient experience seems to support that it is safe to resume treatment once symptoms have resolved completely.
If the ALL is Ph-, most centers are proceeding with standard curative induction therapy because delay is associated with very poor outcomes. The risk of needing an ICU bed during induction therapy is low (probably < 3%). There initially was tremendous controversy about how to manage steroids; however recent studies show that dexamethasone is beneficial in established COVID-19 are reassuring. We therefore feel that since steroids are a crucial part of ALL therapy, they should be used as recommended during induction and intensive post-remission therapy. If patients are at high risk for complications from myelosuppression, some are dose reducing daunorubicin (50%) or using a reduced dose pegaspargase (e.g. 1000 Iu/m2); overall, however, the committee feels that treatment should be given as prescribed Once all induction chemotherapy has been administered, one could consider use of G-CSF to facilitate count recovery. Some are keeping patients hospitalized until count recovery if possible if the inpatient environment is safer than frequent clinic visits. For Ph+ ALL, a TKI with steroids is favored over aggressive multi-agent chemotherapy induction for initial treatment, hoping to avoid prolonged hospitalization during the pandemic.
Intensive post-remission therapy is critical for cure, so we recommend proceeding, with some modifications. Subcutaneous or IV cytarabine may be prepared by pharmacy for home administration (e.g. Days 1-4, 8-11). There is a lot of controversy about rituximab during consolidation – some feel that it should be given with monitoring of IgG levels and replacement; others worried about further exposure in clinics for nurses/patients during the infusion. Consider G-CSF at the end of consolidation and delayed intensification courses to minimize periods of neutropenia.
For patients with high-risk ALL, individualized decision-making regarding transplantation is necessary, balancing the risks of the transplant/COVID-19 against the risk of death from ALL. Many centers are transplanting patients with high-risk ALL.
Are you changing your recommendations for maintenance therapy?
We would recommend trying to stay on schedule for chemo and IT chemo. Some suggest 50% dose reduction of glucocorticoids during maintenance; in many of the European countries, neither prednisone/dexamethasone nor vincristine are included during the maintenance treatment. If a patient becomes COVID+, would hold all maintenance therapy until symptoms are resolved for 14 days. Minimize clinic visits by sending medications to patients and follow them as much as possible via telemedicine and home blood draws.
How are you treating patients with relapsed/resistant leukemia?
For B-ALL: Try to avoid hospitalization by using inotuzumab or quickly transitioning blinatumomab to outpatient (at home with home-care administered bag changes) if possible. Some CAR T-cell trials have re-opened.
For T-ALL: Nelarabine/nelarabine-based regimens may be given as usual.
Patients who achieve CR2 should be considered for allogeneic transplant expeditiously despite the pandemic.
Should ALL patients receive a vaccine for SARS-CoV-2?
In general, it is considered safe and appropriate for patients with ALL to receive vaccines, as long as they are not live, attenuated virus vaccines. Specific to SARS-CoV-2, data regarding the safety and efficacy of vaccines in immunocompromised patients have not yet been released. As a general statement we are likely to support people with ALL receiving a SARS-CoV-2 vaccine (non-live) although they may not mount an effective immune response, but await trial results. For more information about SARS-CoV-2 vaccines and immunocompromised patients, see the ASH FAQs on SARS-CoV-2 vaccines and immunocompromised patients.