The race for survival in myelodysplastic syndromes

Another Summer Olympics has passed and we, like many, trudged into work bleary-eyed each morning, having stayed up late the previous night to watch our favorite events, from swimming to track and field. Hopeful athletes from different countries spend years training to out-swim or out-run their opponents by a few milliseconds. Their build, access to the right coaching and elite genetics all play a role in determining the difference between gold and silver. These attributes are put to the test at the starting line when the gun fires. But how would the outcome of the race be affected if some athletes were to straggle to the starting line later than others?

The epidemiology of myelodysplastic syndromes (MDS) is still in its infancy. Within the United States and Europe, the yearly incidence rate of MDS is approximately 4–4.5/ 100 000 people. MDS is more common in whites compared to African Americans, 3.33/100 000 vs. 2.36/100 000 people, respectively, between the years 2001 and 2003 [1]. For a number of cancers, particularly in the solid tumors – colon, breast, lung, and head and neck – African Americans have inferior survival compared to whites. A multitude of variables are responsible: poor access to cancer screening and treatment, financial and cultural barriers to compliance and health seeking behavior, incipient racial discrimination, and possibly even biology. Any of these factors can lead to less aggressive or less effective treatment among racial minorities and/or people of lower socioeconomic status (SES) [2,3].

Despite the development of multiple prognostic scoring systems in MDS, the influence of demographic factors, such as race and SES, on outcome has been not been studied extensively. In this issue of Leukemia and Lymphoma, Zandberg et al. examine patients who have been referred with an MDS diagnosis to the University of Maryland Greenebaum Cancer Center [4]. This retrospective review of 252 patients seen over a 10-year period reveals that, similar to US Surveillance, Epidemiology and End Results data, black males were diagnosed at a younger age (62 vs. 68 years; p =0.03), and had a longer time to referral (9 vs. 1.5 months; p = 0.03), compared to white males. Despite this, black and white patients did not differ in bone marrow blast counts at diagnosis or referral, cytogenetic findings, frequency of acute myeloid leukemia (AML) progression, or time to hypomethylating agent treatment or hematopoietic stem cell transplant (HSCT). Most strikingly, the longer time to referral was not associated with differences in overall survival.

In contrast, a study of 2570 adult patients with AML treated on Cancer and Leukemia Group B (CALGB – now the Alliance) clinical trials showed that the incidences of good- and poor-risk cytogenetics were higher among African Americans, and African American males (but not females) had worse complete remission rates and overall survival [5]. Following-up on these results, another study tried to determine whether the difference in outcome for African American men resulted from different intensity of post- remission therapy (PRT) [6]. While PRT was significantly delayed (2.73 vs. 1 month, p =0.047) in blacks, they did not receive a different intensity or number of PRT cycles compared to whites. Another study in patients with AML, focusing on SES and the distance a patient travels to a treatment center, reported that these factors were not predictive of outcome in patients with AML receiving remission induction therapy [7]. AML may be the great equalizer, in that the acuity and urgent referral of patients with AML negates the usual prognostic impact of SES, distance from a treatment center and race – unlike with more “chronic” cancers, such as solid tumors.

Other hematologic malignancies, such as monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), do report racial disparity for blacks [8,9]. Blacks have a compromised overall survival over time, even when adjusting for SES, perhaps due to lack of access to chemotherapy, novel drugs and autologous stem cell transplant. Similarly, racial disparities have been seen in HSCT [10,11], for which African Americans are at a disadvantage for donor availability, access to HSCT and treatment-related mortality.

How do we put all of these findings about race and outcome in context? Like MGUS and MM, lower-risk MDS is considered a chronic hematologic malignancy, which generally does not require urgent treatment. Patients have time to seek a second opinion and have the luxury to “shop” for an oncologist. As a result, paradoxically, patients who live a greater distance from a treatment center may actually have a better outcome [12], yet those considered sociodemographically disadvantaged may have a worse outcome, as access to novel medications and clinical trials may be more difficult, and the burden of seeking tertiary care may be placed on the patient him or herself. Meanwhile AML, like higher-risk MDS, is recognized as a medical urgency, prompting a rapid referral to a specialty center for prompt treatment. This may overcome any difficulties in access to medical care. Zandberg and colleagues show that referral patterns of patients with MDS to a tertiary academic institution take longer for younger, black male patients, yet there is no difference in outcome – perhaps because MDS is a mixed bag of both an acute and a chronic cancer, and the study itself does not distinguish between lower- and higher-risk patients.

But at least it is a start. It is troubling that African Americans are delayed in their MDS referrals. While athletes compete against one another in a race for gold, patients should not compete in a race for appropriate therapies and survival.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.