COVID-19 and Adult ALL: Frequently Asked Questions
(Version 1.2; last reviewed September 14, 2020)
Input from Drs. Wendy Stock, Anand Patel, Kristen O’Dwyer, Renato Bassan, Xianfeng Zhou, Xiao-jun Huang, Mark Litzow, Elias Jabbour, Dan DeAngelo, Selina Luger, Nicola Gokbuget, Richard Larson, and Jacob Rowe
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 is tremendous controversy about how to manage steroids. Most agree their use should be minimized (e.g. as anti-emetic therapy) but they are a crucial part of initial ALL therapy. Recent studies showing that dexamethasone can be beneficial in established COVID-19 are reassuring. If patients are at high risk for complications, some are dose reducing daunorubicin (50%) or using a reduced dose pegaspargase (e.g. 1000 Iu/m2). 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 minimal steroid exposure 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?
Consider keeping a higher ANC (~1.0) during maintenance, but otherwise try 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 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.