patient care perspectives

Managing Toxicities From Intensive Induction Therapy for High-Risk MDS and AML

by Courtney D. DiNardo, MD, MSCE

Overview

Younger, more fit patients with acute myeloid leukemia or higher-risk myelodysplastic syndrome may be eligible for intensive remission induction therapy. Such therapy can be highly toxic, often requiring hospitalization for several weeks; however, it may ultimately be curative in a subset of patients.

Expert Commentary

Courtney D. DiNardo, MD, MSCE

Associate Professor
Department of Leukemia
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

“A new diagnosis of a leukemia is certainly life changing. . . . We tell our younger patients who will receive intensive induction treatment that they can usually expect to be in the hospital for approximately 30 days following the start of treatment. . . ."

Courtney D. DiNardo, MD, MSCE

A new diagnosis of a leukemia is certainly life changing. Oftentimes, it takes several days of evaluation to determine exactly what the optimal treatment will be. We tell our younger patients who will receive intensive induction treatment that they can usually expect to be in the hospital for approximately 30 days following the start of treatment, as this is the time frame that is required for the patient's bone marrow to recover from such a regimen. For the patient who presented to the Emergency Department because they felt ill, had bleeding, or had some sort of infection, for instance, and is now told that they will need to be hospitalized for what may be several weeks, this may be quite stressful, as they are often not prepared for such a life disruption.

Patients usually feel all right during the first week of chemotherapy, which is typically a cytarabine and an anthracycline combination. During weeks 2 to 3 of treatment, once the leukemia and normal bone marrow have been cleared out, patients become dependent on blood and platelet transfusions. This is the period in which there is the highest risk of infection. Without intervention, any minor fever or infection can turn into a life-threatening infection within hours in someone without a functional immune system, which underscores the need for hospitalization during treatment. The inpatient setting allows us to start broad-spectrum antibiotics, and we can also promptly take care of the various side effects that may emerge during that period. Typically, during week 4 of treatment, the counts start to recover, and patients begin feeling better and hopefully have gone into a remission. 

In addition to the standard myelosuppression and infections that occur with chemotherapy, we need to ensure that we are evaluating cardiac function if we are administering an anthracycline, which, as previously noted, is very commonly used. We usually do an echocardiogram before we start this treatment because anthracyclines can cause significant cardiotoxicity, especially if there is preexisting cardiac damage.

Another main side effect of an intensive chemotherapeutic regimen that should be highlighted is gastrointestinal related, and this includes nausea, vomiting, and gastrointestinal mucositis. Sore throat and esophagitis can also be seen. Gastrointestinal mucositis is relatively common, and it may cause diarrhea and abdominal pain when it is in the lower gastrointestinal tract. We help manage this with supportive care. Additionally, in a patient with FLT3-mutant acute myeloid leukemia, an FLT3 inhibitor is incorporated into the induction regimen. Midostaurin is approved by the US Food and Drug Administration, and there are currently several clinical trials that are evaluating second-generation agents. FLT3 inhibitors do add a bit to the gastrointestinal toxicity profile of the entire regimen, however. In general, supportive care today is much better than it was decades ago, so patients do not experience the same degree of nausea and vomiting consistently throughout a whole cycle as they may have in the past.

References

DiNardo CD, Garcia-Manero G, Kantarjian HM. Time to blur the blast boundaries. Cancer. 2022;128(8):1568-1570. doi:10.1002/cncr.34119

Kantarjian HM, Kadia TM, DiNardo CD, Welch MA, Ravandi F. Acute myeloid leukemia: treatment and research outlook for 2021 and the MD Anderson approach. Cancer. 2021;127(8):1186-1207. doi:10.1002/cncr.33477

Logan C, Koura D, Taplitz R. Updates in infection risk and management in acute leukemia. Hematology Am Soc Hematol Educ Program. 2020;2020(1):135-139. doi:10.1182/hematology.2020000098

Neuendorff NR, Loh KP, Mims AS, et al. Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper. Blood Adv. 2020;4(4):762-775. doi:10.1182/bloodadvances.2019000955

Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021;35(8):2182-2198. doi:10.1038/s41375-021-01265-7

Wang ES, Baron J. Management of toxicities associated with targeted therapies for acute myeloid leukemia: when to push through and when to stop. Hematology Am Soc Hematol Educ Program. 2020;2020(1):57-66. doi:10.1182/hematology.2020000089

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