Referral patterns and potential barriers to transplantation in patients with MDS

Hematopoietic stem cell transplantation (HSCT) can be a successful treatment for patients with high-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML).¹ However, factors such as age, performance status, comorbidities, and patient frailty may influence transplant referral patterns and outcomes in this population. Currently, the proportion of eligible patients being referred for transplantation is not known in clinical settings.¹

The MDS Hub has previously covered the American Society for Transplantation and Cellular Therapy recommendations for transplantation in patients with MDS. Here we present a summary of the findings from a prospective cohort study on the patterns of consideration for HSCT in patients with HR-MDS and AML.¹ In addition, we also summarize a retrospective study of survival benefits with allogeneic-HSCT (allo-HSCT) versus decitabine, a hypomethylating agent (HMA) agent presented by Runzhi at the European Hematology Association (EHA) 2023.²

Study design¹

This analysis comprised data from the Connect Myeloid Disease Registry (NCT01688011), a multicenter, prospective, observational cohort study in patients with newly diagnosed MDS or AML.¹ Cohorts included patients enrolled at community (CO), government (GOV), or academic (AC) sites. Eligible patients were:¹

• Diagnosed with MDS or AML according to the 2008 World Health Organization criteria;
• ≥18 years of age if diagnosed with MDS or ≥55 years if diagnosed with AML; and
• Enrolled ≥60 days after a diagnosis of MDS or AML.

Patients were assessed for HSCT eligibility at baseline and at each follow-up visit. HSCT eligibility criteria included considered potentially eligible, not considered potentially eligible, or not assessed.

Results

Baseline characteristics

Overall, 778 patients were included, of which 66.3% were from the CO/GOV cohort and 33.7% from the AC cohort.¹ Patients in the AC cohort were younger (p < 0.0001), more likely to reside in the Northeastern United States (p < 0.0001), and more likely to have a private insurance (p = 0.017) compared with the CO/GOV cohort (Table 1).

Table 1. Baseline characteristics*

AC, academic; AML, acute myeloid leukemia; AR, adverse risk; CO/GOV, community/government; HR, higher-risk; IR, immediate risk; MDS, myelodysplastic syndromes. *Adapted from Tomlinson et al.1
Characteristics, % (unless otherwise specified)	CO/GOV cohort (n = 516)	AC cohort (n = 262)
Median age, (range) years	73 (19–97)	69 (34–90)
Sex, male	64.1	62.6
Not specified	8.7	5.7
Primary insurance†
Medicare	66.9	57.0
Private	24.7	32.8
Medicaid	1.6	3.5
Other	6.9	6.6
Overall comorbidity grade
0 or 1	50.8	59.0
2 or 3	49.2	41.0
Diagnosis†
HR-MDS	50.4	30.9
IR-AML	30.2	36.6
AR-AML	19.4	32.4

Transplantation rates and barriers to transplantation¹

• Patients from CO/GOV cohort were less likely to be considered potentially eligible for transplantation compared with those from AC cohort (27.9% vs 43.9%; p < 0.001).
  • Multivariate analysis showed that when adjusted for age (<65 vs ≥65 years) and comorbidity grade (<2 vs ≥2), patients in CO/GOV cohort were less likely to be considered eligible for transplantation compared with AC cohort (odds ratio, 1.6; p = 0.0155).
  • Among patients eligible for transplantation, 45.1% from the CO/GOV cohort versus 35.7% from AC cohort underwent transplantation (p = 0.12).
• From the CO/GOV cohort 50.1% of patients were not considered eligible for transplantation versus 45.4% from the AC cohort. The main reasons for transplantation ineligibility are shown in Figure 1.
• The proportion of patients not assessed for transplantation was higher in the CO/GOV cohort compared with AC cohort (20.7% vs 10.7%, p = 0.0005).

AC, academic; CO/GOV, community/government; ECOG PS, Eastern Cooperative Oncology Group performance status.
^†≥1 is possible.
*Adapted from Tomlinson et al.¹ 

Survival benefit of transplantation versus decitabine²

This was a retrospective study comparing responses to allo-HSCT with decitabine in patients with MDS with increased blasts type I (MDS-IBI). Outcomes included overall survival (OS), event-free survival (EFS), non-relapse mortality (NRM), and cumulative rate of relapse or progression (CIR) at 1 year.

Survival outcomes

• In total, 103 patients were assessed, with a median age of 49 years. Allogeneic HSCT was performed in 61.2% of patients, while decitabine was administered continuously to the remaining 38.8% of patients.

• Patients who underwent allogeneic HSCT versus decitabine treatment had higher OS and EFS rates at 3 years and non-relapse mortality rate after 1 year (Figure 2).
• Cumulative incidence of relapse and progression after 1 year was lower in patients who underwent allo-HSCT versus decitabine treatment.

Allo-HSCT, allogeneic stem cell transplant; MDS-IBI, myelodysplastic syndrome with increased blasts type 1.
*Adapted from Runzhi.¹

Conclusions

The study by Tomlinson¹ showed that many patients who may be potential candidates for allo-HSCT are either not being assessed or considered for transplantation in clinical settings. This suggests the need for increasing resources for transplantation to ensure all patients are appropriately screened and referred for allo-HSCT if appropriate. The study by Runzhi² demonstrates significantly prolonged survival in patients with MDS-IBI who underwent allogeneic-HSCT compared with those administered decitabine.

Together, both studies provide an insight into the success of allo-HSCT and how factors influencing eligibility should be considered in all patients, and patients should not be disregarded ahead of assessment for HSCT due to age and comorbidities.^1,2