The coronavirus disease 2019 (COVID-19) pandemic poses several challenges to the management of patients with leukemia. The biology of each leukemia and its corresponding treatment with conventional intensive chemotherapy, with or without targeted therapies (venetoclax, FLT3 inhibitors, IDH1/2 inhibitors, Bruton's tyrosine kinase inhibitors), introduce additional layers of complexity during COVID-19 highrisk periods. The knowledge about COVID-19 is accumulating rapidly. An important distinction is the prevalence of "exposure" versus "clinical infectivity," which determine the risk versus benefit of modifying potentially highly curative therapies in leukemia. At present, the rate of clinical infection is < 1-2% worldwide. With a mortality rate of 1-5% in CO-VID-19 patients in the general population and potentially of > 30% in patients with cancer, careful consideration should be given to the risk of COVID-19 in leukemia. Instead of reducing patient access to specialized cancer centers and modifying therapies to ones with unproven curative benefit, there is more rationale for less intensive, yet effective therapies that may require fewer clinic visits or hospitalizations. Here, we offer recommendations on the optimization of leukemia management during high-risk COVID-19 periods.
The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. The notable subsets of AML include acute promyelocytic leukemia (APL), core-binding factor AML (CBF-AML), AML in younger patients fit for intensive chemotherapy, and AML in older/unfit patients (usually at the age cutoff of 60-70 years). We also consider within each subset whether the AML is primary or secondary (therapy-related, evolving from untreated or treated myelodysplastic syndrome or myeloproliferative neoplasm). In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80%. Treatment of CBF-AML with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin (GO) results in estimated 10-year survival rates of ≥75%. In younger/fit patients, the "3+7" regimen (3 days of daunorubicin + 7 days of cytarabine) produces less favorable results (estimated 5-year survival rates of 35%; worse in real-world experience); regimens that incorporate high-dose cytarabine, adenosine nucleoside analogs, and GO are producing better results. Adding venetoclax, FLT3, and IDH inhibitors into these regimens has resulted in encouraging preliminary data. In older/unfit patients, low-intensity therapy with hypomethylating agents (HMAs) and venetoclax is now the new standard of care. Better low-intensity regimens incorporating cladribine, low-dose cytarabine, and other targeted therapies (FLT3 and IDH inhibitors) are emerging. Maintenance therapy now has a definite role in the treatment of AML, and oral HMAs with potential treatment benefits are also available. In conclusion, AML therapy is evolving rapidly and treatment results are improving in all AML subsets as novel agents and strategies are incorporated into traditional AML chemotherapy.
Skin infiltration with B-lymphocyte chronic lymphocytic leukemia (B-CLL) is rare. In contrast to Richters transformation of CLL or myeloid leukemias, skin involvement in CLL may be consistent with prolonged survival, as illustrated by the currently reported two cases. As in these patients, local therapy for skin disease may delay or obviate the need for systemic therapy in B-CLL.
The advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML) has dramatically changed the management of patients with CML. With continuous long-term TKI therapy, CML can be managed like a chronic condition, and most patients can expect to have a normal life expectancy. Given the prospect of lifelong therapy, however, issues related to adherence become particularly important and warrant greater attention since attainment of favorable long-term survival depends in large part on consistent, appropriate treatment administration over years, if not decades. As the multidisciplinary care team approach to cancer care has gained traction at academic centers and community practices, midlevel providers, including nurse practitioners and physician assistants, have taken on greater patient-related responsibilities. Midlevel providers have the potential to foster and maintain meaningful provider-patient relationships that may span years, and are well positioned to recognize and manage problems that patients may have with adherence. Here we discuss the importance of achieving and maintaining responses to TKI therapy, describe the clinical consequences of poor adherence to TKI therapy in CML, and outline factors behind poor adherence. We also share strategies that we use at our center to improve adherence to long-term TKI therapy for CML.
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