Should Myelodysplastic Syndromes in Very Old Patients be More Actively Managed? Clinical Characteristics, Management and Outcomes for Patients 85 Years and Older

Introduction

Myelodysplastic Syndrome (MDS) is classically a disease of older people, with median age at presentation of 70-75 years. The incidence of MDS is estimated at 5-13/100,000/year, but rises to >20/100,000/year in older populations. An increase in diagnosis over the last decades is in part due to improved recognition of MDS, but likely also to an increase in the ageing population. There is very little data on the clinical course, management and outcomes for very old patients (≥85 years of age) with MDS.

Patients and Methods:

This was a retrospective, multicentre analysis of 84 patients with MDS or Chronic Myelomonocytic Leukemia (CMML) aged ≥85 years at diagnosis from 6 centres in Ireland.

Results:

We identified 84 patients aged ≥85 years at time of diagnosis of MDS (n= 70) or CMML (n=14), including 47 men (56%) and 37 women (44%). Median age at diagnosis was 87 years (range 85-98). Most patients (93%) were anemic at presentation, including 45/47 men (96%) and 33/37 women (89%). Median hemoglobin (Hb) was 9.5 g/dl (range 5.9 -13.8). Median neutrophil count was 2.4 x10⁹/L (range 0-72). Forty-four patients had thrombocytopenia (median platelet count 144 x 10⁹/L (range 18-624)). Data regarding co-morbidities were available for 75 patients: 69% had hypertension, 36% ischemic heart disease, 39% atrial fibrillation, 31% heart failure, 19% diabetes and 39% renal dysfunction. Ferritin was elevated in 18 (32%) of 57 patients tested. 2006 WHO subgroups were reported for 81 patients: RCMD (32; 40%), CMML (14; 17%), RA (10; 12%), RAEB-1 (10; 12%), RAEB-2 (7; 9%), RARS (2; 3%), t-MDS (2; 3%), Hypoplastic MDS (1; 1%) and 5q- Syndrome (1; 1%).

Cytogenetic analysis was performed in 49 patients (58%); results were available for 39 (46%). No patient had molecular studies for MDS-associated mutations or p53 deletions/mutations. Karyotype was normal in 23 patients (59% of those with results available), deletion Y in 5 (13%), Trisomy 8 in 5 (13%), complex in 3 (7.7%), 5q- in 2 (5.2%), and monosomy 7 in 1 (2.5%). Risk stratification by IPSS-R was available for only 37/84 patients, primarily due to lack of cytogenetic testing.

Data were available regarding treatment strategies for 81 patients. Thirty-five (43%) received supportive care only. Forty-five patients (57%) were transfused; 29 (34%) became transfusion-dependent during the course of their disease. Of these, only 14 (48%) received erythropoietin (EPO). Of 50 patients with significant anemia likely to cause symptoms (Hb < 10g/dl), only 21 (42%) received EPO. Five patients (6%) received azacitidine (1-18 cycles; median 5), 7 (8%) received G-CSF; none received lenalidomide or iron chelation. Median survival for all patients was 17 months (range 0-147), 16 months for men (range 0-70), and 27 months for women (range 1-147). In 35 patients who had IPSS-R data available, median survival was 49 months for Very Good, 30 months for Good and 13 months for Intermediate category patients. For 4 patients in the Poor and Very Poor categories median survival was 1, 5, 7 and 28 months. Median survival for patients with RA was 28 months (n=10), RCMD 25 months (n=29), CMML 13 months (n= 14), RAEB-1 10 months (n=10) and RAEB-2 19 months (n=7). Six patients (including 3 with RAEB-1, 1 with CMML and 1 with t-MDS) developed Acute Myeloid Leukaemia (7%) at a median of 4.5 months from diagnosis. Median survival for these patients was 9.5 months. Of 84 patients, 60 have died. The main causes of death included marrow failure, sepsis, cardiac events, other malignancies and gastrointestinal bleeding.

Conclusions

Anemia is the commonest presenting feature of MDS in the very old, and may be the sole cytopenia. Unexplained anemia in the very old should trigger suspicion of underlying MDS, especially if associated with a high MCV. In many patients over 85 years cytogenetic analysis is not performed, precluding accurate prognostic evaluation. MDS in these very old patients is not often actively managed with pharmacological intervention or chemotherapy. Up to 50% of transfusion-dependent patients do not receive erythropoeitin. Azacitidine and lenalidomide are infrequently used. Co-morbidities (especially cardiac and renal disorders) are very common. Survival can be prolonged, especially in patients with low-risk disease. With an ageing population, management of very elderly patients with MDS is becoming more challenging and a more proactive approach should be considered.

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