Perspectives of caregivers of older adults with acute myeloid leukemia during initial hypomethylating agents and venetoclax chemotherapy

Abstract

Background

Older adults with AML commonly receive a hypomethylating agent (HMA) as first-line therapy. The addition of venetoclax (VEN) to HMAs has been shown to improve remission rates and overall survival. The use of combination therapy (HMA + VEN) requires frequent follow-up, results in longer infusion times, and likely increases caregiver responsibility at home. We describe experiences of informal caregivers (family/friends) providing care to older adults with AML receiving HMA + VEN.

Methods

Fourteen caregivers of older adults with AML receiving HMA + VEN (September 2020 to September 2021) were recruited as part of a control group of an ongoing NIH-funded clinical trial. Semi-structured interviews were conducted to gain initial insight into caregiver experiences at the start of HMA + VEN treatment. Two researchers analyzed the data using thematic content analysis. Data saturation occurred when no new themes were found in subsequent interviews, but all interviews were coded and synthesized.

Results

Of the 14 caregivers interviewed, the majority were spouses (n = 10), female (n = 13), and aged 45 to 83 (median age 65). We identified five themes: (1) the impact of an AML diagnosis in older adulthood, (2) care recipient condition changes, (3) perspectives of caregiving roles and tasks, (4) factors influencing caregiving experiences, and (5) support system roles.

Conclusions and implications

Caregivers for older adults with AML report a range of experiences navigating health systems, caregiving responsibilities, and resource needs. The risk for caregiver burden and unmet needs should be addressed to improve caregivers' abilities to provide care.

Introduction

Caregivers of older adults with acute myeloid leukemia (AML) may be more necessary given the recent advances in treatment and the resulting shifting of care from inpatient to outpatient. Traditionally, high-intensity treatments for AML could not be given to older adults because they were less likely to survive, and when given, these treatments often required long hospital stays that produced significant amounts of patient distress. Fortunately, treatment has changed over the last few years with long-term survival and complete remission rates of up to 70% for older adults achieved through the hypomethylating agents and venetoclax (HMA + VEN) chemotherapy regimen [1–4]. HMA + VEN treatment sometimes requires hospital admission to monitor for adverse side effects such as tumor lysis syndrome and always requires frequent outpatient follow-up. Caregivers provide essential support from the time of initial diagnosis to active treatment and survivorship.

Caregivers of those with leukemia are particularly vulnerable to psychosocial distress [5, 6]. Individuals with hematologic cancers and their caregivers describe a high prevalence of anxiety, depression, and financial burden [7–10]. Caregivers are often responsible for many tasks for the patient and home, including, but not limited to, psychosocial support, symptom management, medication management, and transportation. Furthermore, caregivers have to manage the coordination of appointments and assist with activities of daily living [5]. Older adults with AML are more likely to have multiple comorbidities at baseline and subsequent functional decline and adverse effects related to treatment along with multiple comorbidities at baseline [11]. These limitations in function and symptoms coupled with existing responsibilities often contribute to psychosocial stress and emotional distress for caregivers which have been further exacerbated by the COVID-19 pandemic [9, 12].

Newer treatments like HMA + VEN may necessitate a higher level and prolonged duration of caregiving responsibilities compared to prior traditional regimens that were primarily given to inpatient. Though the regimen is lower intensity, there remains the risk of life-threatening side effects, including the risk of infection and tumor lysis syndrome [13]. HMA + VEN is given monthly for an indefinite time (i.e., treatment continues until the progression of the disease). Although we know decline in physical function can be stressful to both patient and caregiver, it is unknown how this treatment impacts caregivers’ experiences providing care to this population. At present, neither quantitative nor qualitative studies have yet described the experiences of caregivers of older adults with AML receiving HMA + VEN and their observations of the patient’s condition while receiving this regimen. Considering the potential burden on caregivers of this population, our purpose for this paper was to describe the experiences of informal caregivers (family/friends) providing care to older adults with AML after receiving their first cycle of HMA + VEN.

Methods

Design

A qualitative descriptive design was used to characterize the experiences of caregivers of older adults with AML after the first cycle of HMA + VEN chemotherapy. This study used baseline (cycle 1 of HMA + VEN) interview data. The study was approved by the local Institutional Review Board (IRB 18–3244).

Setting and sample

The study was conducted at a southeastern US public safety net comprehensive cancer hospital. A convenience sample of fourteen caregivers of older adults with AML receiving a chemotherapy regimen of HMA + VEN as part of their cancer treatment was recruited between September 2020 and September 2021 for the control group of the ongoing Palliative and Supportive Care inTervention (PACT) study (NCT04570709).

Data collection

Semi-structured interviews were conducted by two research team members (YNC, ALB) after cycle 1 of HMA + VEN to gain insight into experiences, observations, and challenges related to caring for an older adult during chemotherapy, in inpatient and outpatient settings, and at home. Two questions were asked during interviews: “What do you wish you had known about [care recipient’s name]’s acute leukemia?” and “What else might have been helpful to you during the [hospitalization/clinic visit]?” Probing questions were then asked to expand on caregivers’ responses to the interview questions. Interviews ranging in length from 5 to 33 min were conducted in a private room, digitally recorded, and stored on a secure university server.

Data analysis

Each interview recording was transcribed verbatim by a third party and de-identified by three research team members (EP, KI, KS) in Microsoft Word. Transcripts were analyzed to answer the following research question: What are the initial experiences of caregivers of older adults with AML after one cycle of HMA + VEN. We used the thematic content analysis method for data analysis [14]. KI and KRT independently coded three interviews, codes and excerpts were pooled in Microsoft Excel, KRT reviewed excerpts and codes for discrepancies, KI and KT coded the remaining interviews, and KT and ALB created a preliminary list of themes, and themes were then discussed and refined by ALB, KRT, and KI. Themes were identified by examining codes for patterns and similarities.

Results

Of the 14 caregivers, the majority were spouses (n = 10), female (n = 13), and aged 45 to 83 (mean age 65.64; SD = 9.3; Table 1). We identified five major themes from baseline interviews: (1) the impact of an AML diagnosis in older adulthood, (2) expected and unexpected patient condition changes, (3) perspectives of caregiving roles and tasks, (4) facilitators and barriers to caregiving, and (5) support systems (Table 2).

Table 1.

Participant demographics

Characteristics		Caregivers (n = 14)
		n (%)
Gender	Male	1 (7.1)
	Female	13 (92.7)
Race	Black or African American	1 (7.1)
	White	13 (92.7)
Ethnicity	Non-Hispanic	12 (85.7)
	Prefer not to answer	1 (7.1)
	Missing	1 (7.1)
Education level	9th–11th grade	1 (7.1)
	High school graduate/GED	3 (21.4)
	College degree	6 (42.9)
	Advanced degree	4 (28.6)
Annual household income	< $20,000	1 (7.1)
	$20,001–40,000	1 (7.1)
	$40,001–60,000	1 (7.1)
	$60,001–80,000	3 (21.4)
	$80,001–100,000	0 (0)
	> $100,001	6 (42.9)
	Prefer not to answer	2 (14.3)
Marital status	Single/Never Married	1 (7.1)
	Married/Partnered	12 (85.7)
	Divorced	1 (7.1)
Relationship	Spouse	10 (71.4)
	Child/Children	4 (28.6)
Distance from cancer center	> 50 miles	7 (50)
	< 50 miles	7 (50)

*Distance from the cancer center was calculated from zip code data

Table 2.

Themes, subthemes, and exemplar quotes

Theme	Subtheme	Exemplars
Unexpected diagnosis of AML in older adulthood	Symptoms of aging versus AML	• I expected something to break and so I guess this just happened to be it • He had gone through a cancer screen back in October and passed that with flying colors. So, when he initially was not feeling good, we had no idea that it could be something like this
	Older adulthood	• Being such an independent person and then all of a sudden you’re so reliant on other people, how did that have to feel? But networking with other people, I guess for the most part it’s inevitable
Caregiver’s observations of care recipient changes	Physical condition changes	• I don’t think he has the strength really to do it and also he would ask me for a glass of water and the refrigerator is really near or something
	Cognitive Impairment	• He seemed like he wasn’t in the room at that moment. Yeah. But not like he lost conscious
	Side effects of chemotherapy: Reality vs. expectations	• He’s had zero nausea. All of the side effects they said he could have, he’s had them to some degree, but that was very transparent, very well communicated, and then what he should do to try to counteract them was very well communicated as well
Perspectives of caregiving roles and tasks	Physical care	• So I’ll be aware of things like that, that he might not be aware of. We had some work done in the backyard and I said, “You can't go out there and play in that dirt with that man.” He is kicking up dust. You can't be out there
	Psychological care	• My job is to keep him from feeling anxious, so I take care of making sure they’ve got all their meals planned and those kinds of things and just anything that causes him anxiety
Factors influencing the caregiving experience	Helpful factors to caregiving	• It’s lucky that we’re both retired, and we don’t have other responsibilities that we had to separate from in order to concentrate on this, which has to have our full concentration
	Barriers to caregiving	• We were challenged with care for my mother who was battling dementia and Parkinson’s… There were a lot of bad days that, –there were days that I had both parents in the hospital at the same time
Support systems	Logistical Support	• I do have a brother…Our personalities are different too so I’m the decision maker…whatever I ask (him) to do, he does
	Social support	• In addition to speaking to the physicians and everybody else there at the [cancer hospital] when we had certain appointments, of course I went online and did some research

Unexpected diagnosis of AML in older adulthood

Six caregivers described aspects of the AML diagnosis in relation to older adulthood. Caregivers reported that some initial symptoms of AML were mistaken for natural signs of aging and that being an older adult created complexities in needs. For example, some caregivers “expected something to break” because of older age “and this just happened to be it.” In other cases, the diagnosis came as a surprise to caregivers. Though all caregivers experienced shock over receiving the diagnosis of AML, some described feeling that a sudden change in health status was inevitable in the setting of advanced age.

AML symptoms that were initially interpreted as common symptoms of aging included fatigue, gastrointestinal upset, and dental problems. Caregivers also described changes in cognitive abilities. One stated, “I noticed that the hardest parts with dad being eighty-eight are that he doesn’t process as fast.” The caregiver noted that these changes could be a reflection of age-related cognitive decline, treatment-related side effects, or both.

One caregiver recalled that people noticed and remarked upon changes in the time before diagnosis: “It kind of got on his nerves because everybody was saying something, about him looking different.” In contrast, several caregivers described experiencing shock when the diagnosis came shortly after a clean bill of health had been received from the care recipient’s primary care team. “He had gone through a cancer screen back in October and passed that with flying colors. So, when he initially was not feeling good, we had no idea that it could be something like this.”

Caregiver’s observations of care recipient changes

Three caregivers described profound changes in the care recipient’s energy, motivation, and tolerance for physical activity. When patients gave up activities, they previously enjoyed; it raised concerns about serious changes in health status. For example, one caregiver said “He doesn’t mow his yard anymore. Somebody else does that. And when I saw him give that up, I knew how bad he must feel.” Another caregiver described that the care recipient “had been a very strong man, a very active man and now he is very weak.”

Several caregivers had expectations about chemotherapy side effects (such as hair loss) based on knowledge gained from previous experiences. Caregivers also described that many of the side effects they expected never presented.

Perspectives of caregiving roles and tasks

Participants described their caregiving role in terms of physical and psychological care. Physical support provided to care recipients occurred in the context of the COVID-19 pandemic and older adulthood and seemed to focus on protecting the care recipient from infection and problem-solving mobility issues. Immunosuppression resulting from advanced age, leukemia, and chemotherapy combine to create a significant risk for infection, Physical care included adopting neutropenic precautions (e.g., avoiding going out, isolating and/or maintaining a safe distance from others), monitoring for signs of infection such as fever by taking temperatures, and problem-solving mobility issues. For example, one caregiver noted getting his father new shoes to solve mobility issues, “I said this is really not very stable and safe because you’re walking around with shoes that aren’t tied, but they’re supposed to be tied. So, I ordered him some slip-on tennis shoes that are also about half the weight too, so we’ll see if that makes a difference for him”.

Psychological needs such as increased vulnerability from immobility and immunosuppression created anxiety and isolation. For example, one participant shared “the younger grandchild, he held a fever and … we could not go to see him …and (Patient) was very sad about it.” Another participant shared, “I mean if we could just somehow minimize the exposure and the waiting around and the time and especially during COVID. He doesn’t want to be around anybody else. Everybody scared the [expletive] out of him that he shouldn’t be and then the first thing we do is we put him in an environment where there are a lot of people so that gives him anxiety.”

Caregivers reported providing psychological care, including encouraging their care recipient, managing their anxiety, and limiting potential distress. For example, one participant said, “My job is to keep him from feeling anxious so I take care of making sure they’ve got all their meals planned and those kinds of things and just anything that causes him anxiety, I want to jump on it right away.” Another caregiver described, “When he gets a little depressed, I try to do funny things and help him out there because I know what it’s like to be depressed.”

Factors influencing the caregiving experience

All caregivers identified factors that influenced their caregiving experience including factors that were helpful and factors that made caregiving more challenging. Helpful factors included being retired or having job flexibility, clustering outpatient appointments, and previous caregiving experience. Some caregivers described effective coping mechanisms they had developed during prior difficult experiences in their lives that came “naturally” to them in their current situation. Experienced caregivers found it easier to perform their roles because of pre-existing proficiency in strategies such as organizing and managing complex medication regimens. One caregiver said she could “remember pills and how long he takes them” because she had prior caregiving experience.

Challenges included long wait times in outpatient clinics, COVID-19, having multiple caregiving responsibilities, and not having enough time to care for themselves and their care recipient. Three caregivers described that long clinic wait times were frustrating. One likened the experience to taking a long-distance flight, “Your actual flight time is only five hours or maybe it’s twenty hours of flight time to get to the other side of the world, but it takes you forty because you’re waiting in between everything.” Another caregiver said, “It’s just here waiting for so long for everything, and there’s always a problem” and “it gets very aggravating and stressful, just waiting for hours… for a small little something.” Several caregivers noted that caring for two older adult parents was challenging, stating that “there were a lot of bad days… days where I had both parents in the hospital at the same time.” Another caregiver described that there just was not enough time to get support for themself, “I mean there’s hardly any time to add another person who could counsel because there’s just so many hours in the day, and they’re very filled up here with a situation like leukemia.”

The COVID-19 pandemic created barriers to access to in-person dental or primary care that may have facilitated an earlier diagnosis of AML and offered caregivers additional education and support.

Support systems: social support and logistical support

Caregivers described a variety of needs, including medical information about AML, information about HMA + VEN treatment, and accessing social support. Caregivers sought information about whether AML could appear suddenly, how AML presents, and what to expect their care recipient to experience as they received chemotherapy. One caregiver noted, “You know if you could talk with another caregiver, that might be nice. But everybody’s experience is different.” Caregivers who were not spouses of the care recipient (e.g., adult children) described seeking information on Wikipedia and Google, whereas caregivers who were older adults described talking to the health care team for this information.

Discussion

We examined the experiences of caregivers of older adults with AML receiving HMA + VEN. We found that caregivers’ experiences varied in terms of context, but there were common themes including AML diagnosis that was unexpected/shocking; care provided included protecting the care recipient from illness, and caring for an older adult came with complex challenges (e.g., caring for another older adult parent, being an older adult themselves). To our knowledge, this is one of the first studies to explore caregivers’ perspectives while caring for their loved ones who received their first cycle of HMA + VEN. Our findings highlight the need for early intervention surrounding the initiation of HMA + VEN therapy regarding the need for information about AML disease characteristics and therapy (i.e., what to expect during treatment, expected duration of care), as well as clinical support for managing distress and caregiving burden.

Our findings are similar to other AML caregiving studies focused on psychological, physical, and information needs for support [15, 16]. Caregivers in our study described similar caregiving responsibilities to other AML caregivers, but in this study, we found caring for an older adult was accompanied by patient needs, such as physical decline related to cancer treatment and cognitive decline. Some literature suggests that older adults with AML have different care needs compared to young or middle-aged adults with AML [16, 17]. Older adults with AML are more at risk for fragility and mobility issues compounded with the natural course of aging and can be even more susceptible to infectious diseases [18, 19]. Caregivers of older adults with AML may provide different levels and types of support, especially if the patient has severe levels of fatigue, decreased dependence, and physical mobility difficulties [18]. Therefore, caregivers of older adults with AML may require additional training on managing fatigue and mobility issues at home than caregivers of younger adults with AML.

Our sample included four adult children who provided care to their older adult parents with AML. Differences between spouses and adult children providing care have been noted in qualitative work in individuals with AML who are less than 65 years old [20]. Kastrinos and colleagues noted that adult children providing care experienced relational shifts where they “became the parent,” which is consistent with the experiences of adult children in our sample. Caregivers in our sample described caring for another older adult or their children while also caring for the older adult with AML. Adult children providing care to an older adult parent with AML may require additional support in managing care for multiple individuals.

Lastly, spousal caregivers are more likely to be older adults themselves, which may present unique challenges related to the caregiver’s health status. Caregivers who are also older adults may have their ability to provide care impacted by how they can respond to the physical tasks of caregiving because of their potential physical frailty [21, 22]. Spousal caregivers in our sample described that being older meant they often had sufficient time to provide care if they were retired and often had more life experiences related to caregiving, which they viewed as beneficial to their ability to provide care.

This study evaluated caregivers’ perspectives after the first cycle, and their experiences are expected to change over the course of treatment and beyond. This may be particularly true with HMA + VEN because treatment is given monthly and indefinitely (i.e., evidence of disease progression) prolonging the duration of time and adding uncertainty to the “end” of treatment (e.g., transition to the end-of-life care) and of caretaking that patients require support [23]. Indeed, close attention to what the caregivers are going through at each stage may inform providers to customize and modify interventions to minimize caregiver uncertainties, distress, and risk for burnout.

Implications for research and policy

All caregivers require varying degrees of support and interventions should meet caregivers where they are in terms of self-efficacy, caregiving experiences, time in their lives, and care recipient needs. An AML diagnosis in older adulthood may warrant assistance that is not covered by Medicare and/or Medicaid (e.g., extensive caregiving education, personal care or respite services, psychological support, and anticipatory grief counseling). As the population of care recipients and caregivers becomes older, Medicare and/or Medicaid expansion specific to the support of caregivers may be needed. Advances in AML treatment for older adults may increase a person’s life span but may also increase the caregiving-related burden. Supportive care interventions should be tailored to the individual caregiver within their context (e.g., a spouse versus an adult child). Particular attention should be given to caregiver populations at higher risk for negative effects of caregiving (e.g., caregivers who are also older adults) and additional rehabilitative services for older adults with cancer aimed at maintaining or improving quality of life and decreasing caregiver burden [24].

The Caregiver Advise Record Enable Act has been passed in forty-four states [25] and requires documentation of the primary caregiver in the electronic medical record. However, policies are needed that go beyond documentation to increase support for medically and physically fragile older adults with cancer and their caregivers. Foundational policies like the Build Back Better Framework begin to address caregiver needs by proposing expanding access to home and community-based services for older Americans [26]. However, expansion of access to health care services requires a concomitant expansion in the home and community-based workforce. Policies providing a living wage to caregivers providing at-home care may alleviate some financial burdens and enable caregivers to continue providing support.

Strengths and limitations

Our study had several strengths in terms of sample diversity. One noticeable strength was that our sample included seven caregivers traveling more than 50 miles one way to the cancer hospital, representing geographical diversity. However, caregivers traveling a distance to a cancer center may experience a greater caregiving burden related to time, transportation, and rurality. Secondly, we had two distinct groups of caregivers in the sample representing a wide spectrum of education and income; 4 caregivers had a high school/GED education or less, and 10 caregivers had a college or advanced degree. Six caregivers had an annual household income of > $100,001. The third strength was our ability to capture the caregivers’ perspective at the end of HMA+VEN cycle 1 treatment, allowing for insights into the complexities of caregiving at this specific time.

Our study has limitations worthy of discussion. First, though our data reached saturation for many themes, the qualitative study design and the small sample do not allow for generalizability. Second, all participants were treated and recruited at one southeastern US public safety-net hospital. Our comprehensive cancer center is racially and ethnically diverse; however, in our sample, 13 of 14 participants were women, and 13 of 14 participants were white. The lack of racial, ethnic, and cis-gender diversity is a limitation and requires additional effort to recruit a diverse sample of caregivers (informal and formal) for future studies. Third, we report only on the baseline interview, limiting understanding of the comprehensive changes in caregivers’ experiences over time. Fourth, six of the interviews were short in duration (less than 9 min long) which could have impacted the depth of information provided by participants. However, even in the six shorter interviews, caregivers were detailed in describing their experiences, and the majority of the interview was the participant speaking. Last, in several cases, the caregiver did not wish to leave their care recipient during the interview, which may have introduced social desirability bias. Of the 14 participants, 9 did not want to leave the care recipient, with the majority being female caregivers. In scenarios where caregivers are so heavily relied upon, they rarely want to leave the care recipients’ side. This presents an ongoing challenge in this research space, and flexibility is needed to meet caregivers where they are. Despite this limitation, the majority of participants openly discussed their emotions and experiences even with the care recipient present.

Conclusion

In this study, we describe the experiences of caregivers of older adults with AML receiving a new chemotherapy regimen, HMA + VEN. Caregiving for an older adult presents challenges such as managing the side effects of treatment in tandem with the natural effects of aging (e.g., frailty and cognition changes). Caregivers’ experiences may differ based on their relationship to the care recipient, and specific challenges may be present for adult children who are caring for two older adults or the older adult with AML and their children.

Author contribution

All authors provided substantial contributions to the conception, design, and acquisition of data; analysis and interpretation of data; and writing, review, and approval of the final manuscript.

Funding

The primary study was funded by the National Institutes of Health National Institute of Nursing Research (R34NR019131: PI Bryant) and the Lineberger Developmental Grant Program. During the writing of this manuscript, Dr. Tan was supported by the National Institutes of Health National Cancer Institute as a post-doctoral fellow in the Cancer Care Quality Training Program (T32CA116339); Dr. Chan was supported by the American Cancer Society Doctoral Degree Scholarship in Cancer Nursing, Alpha Alpha Chapter of Sigma Theta Tau International Honor Society of Nursing Research Grant, and UNC School of Nursing Elizabeth Scott Carrington Nursing Scholar (2021–2022). Elissa Poor was supported by the Gayle Collier Robbins Cancer Fund Scholarship (2021–2022) and the M. L. Reynolds Gray Endowed Nursing Scholarship (2021–2022) through the UNC School of Nursing. Stephanie Betancur was supported as a pre-doctoral trainee on the National Institute of Nursing Research training grant Interventions for Preventing and Managing Chronic Illnesses (T32NR007091), and through the Jonas Nurse Leaders Scholars Program (Environmental Health), the Hillman Scholars Program in Nursing Innovation, and Elizabeth Scott Carrington Nursing Scholarship.

Data availability

No data is publicly available.

Code availability

Submit code requests to the corresponding author.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval

Ethical approval was received from University Institutional Review Board (IRB #18–3244) prior to study initiation.

Consent to participate

Informed consent was obtained from all participants.

Consent for publication

All participants consented to publication.

Conflict of interest

The authors declare no competing interests.