Objectives

The lower morbidity and mortality of reduced-intensity conditioning (RIC) regimens have allowed allogeneic hematopoietic cell transplantation (HCT) in older patients. However, there are only limited data on the feasibility and outcomes of URD HCT in elderly patients.The aim of the study was to compare the outcome in OS and PFS for patients transplanted using unrelated donor (URD) in patients age 60 or older.

Patients and methods

We retrospectively analyzed outcomes in 62 consecutive hematologic malignancy patients aged > or =60 years (median, 62 years; range: 60-70 years) undergoing reduced intensity conditioning regimens (RIC) from URD. In this study, URD was used only when a MRD was not available.

Then we compared the outcome of 17 elderly patients (age >65 years) with 44 younger patients aged between 60 and 65 years. Patient, disease and transplant characteristics are shown in Table 1.

Table 1

Study population characteristics

All patients (n=61)Age>60<65 (n=44)Age=>65 (n=17)P value
n%n%n%
Age        
 Median [range] 62 [60-70] 62 [60-64] 66 [65-70] <0.001 
Diagnosis       0.314 
 Acute leukemia/MDS 38 62 25 57 13 76 
 Lymphoma/CLL 12 20 11 25 1 6 
 Multiple Myeloma 4 7 2 5 2 12 
 Myelofibrosis 5 8 5 11 0 0 
 CML 1 2 1 2 0 0 
 Aplastic anemia 1 2 0 0 1 6 
Disease risk index       0.216 
 Low 9 15 8 18 1 6 
 Intermediate 38 63 25 57 13 77 
 High 13 22 11 25 2 12 
 Very High 0 0 0 0 0 0 
HLA compatibility       0.281 
 10/10 53 87 37 84 16 94 
 9/10 8 13 7 16 1 6 
Graft source       0.632 
 PBSC 58 95 42 95 16 94 
 BM 3 5 2 5 1 6 
Conditioning regimen       0.014 
 Flu-Bu 51 84 38 86 13 76 
 Flu-TBI 3 5 1 2 2 12 
 Other 7 11 5 11 2 12 
ATG       0.062 
 Yes 57 93 43 98 14 82 
 No 4 7 1 2 3 18 
GVHD prophylaxis        
 CsA 49 80 37 84 12 71 0.200 
 CsA + MMF 12 20 7 16 5 29  
HCT-CI[DB1]       0.290 
 0-2 32 56 21 52 15 88 
 =>3 25 44 19 48 2 12 
 Unknown 4  4  0  
Follow up       0.030 
 Median [range] 36 [5-74] 40 [7-74] 13 [5-66] 
All patients (n=61)Age>60<65 (n=44)Age=>65 (n=17)P value
n%n%n%
Age        
 Median [range] 62 [60-70] 62 [60-64] 66 [65-70] <0.001 
Diagnosis       0.314 
 Acute leukemia/MDS 38 62 25 57 13 76 
 Lymphoma/CLL 12 20 11 25 1 6 
 Multiple Myeloma 4 7 2 5 2 12 
 Myelofibrosis 5 8 5 11 0 0 
 CML 1 2 1 2 0 0 
 Aplastic anemia 1 2 0 0 1 6 
Disease risk index       0.216 
 Low 9 15 8 18 1 6 
 Intermediate 38 63 25 57 13 77 
 High 13 22 11 25 2 12 
 Very High 0 0 0 0 0 0 
HLA compatibility       0.281 
 10/10 53 87 37 84 16 94 
 9/10 8 13 7 16 1 6 
Graft source       0.632 
 PBSC 58 95 42 95 16 94 
 BM 3 5 2 5 1 6 
Conditioning regimen       0.014 
 Flu-Bu 51 84 38 86 13 76 
 Flu-TBI 3 5 1 2 2 12 
 Other 7 11 5 11 2 12 
ATG       0.062 
 Yes 57 93 43 98 14 82 
 No 4 7 1 2 3 18 
GVHD prophylaxis        
 CsA 49 80 37 84 12 71 0.200 
 CsA + MMF 12 20 7 16 5 29  
HCT-CI[DB1]       0.290 
 0-2 32 56 21 52 15 88 
 =>3 25 44 19 48 2 12 
 Unknown 4  4  0  
Follow up       0.030 
 Median [range] 36 [5-74] 40 [7-74] 13 [5-66] 

Legend:MM, multiple myeloma; MDS, myelodysplastic syndrome; MF, myelofibrosis; CLL, chronic lymphocytic leukemia; PBSC, peripheral blood stem cells ; BM, bone marrow ; Flu, fludarabine; Bu, busulfan; ATG, antithymocyte globulin; GVHD, graft versus host disease; CSA, cyclosporine A; MMF, mycophenolate mofetyl; HCT-CI, HCT comorbidity index score.

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Results

No patients experienced graft rejection. The median HCT comorbidity index score was 2 (range, 0 to 6). With a median follow up of 36 months (range, 5-74), the cumulative incidence of grades II to IV acute GVHD was 28% and of grades III to IV acute GVHD, 13%. At 2 years, the cumulative incidence of chronic GVHD was 27%, progression-free survival (PFS) was 62%, overall survival (OS) was 63%, and relapse was 14%. Non relapse mortality (NRM) was 24% at 2 years.

The cumulative incidence of grade II–IV Acute GVHD was 43% for the younger group and 17% for the older group (P = 0.056). The cumulative incidence of chronic GVHD was not different between the two groups (23% vs. 45% (p=0.3), respectively). Two-year OS and PFS was 57% versus 86% (P = 0.059) and 55% versus 86% (P = 0.03), in the younger and the older group respectively. The 2-year NRM and relapse was 26% versus 14% (P = 0.4) and 19% versus 0% (P = 0.04), in the younger and older group respectively.

Conclusions

This retrospective study suggest that RIC HCT from URD is a safe and effective option for patients aged > or =60 years or older, and in the absence of suitable related donors, well-matched URD may offer a very reasonable alternative, and that does not appear to be associated with a detrimental outcome. However these results are encouraging showing once again that with an adequate selection, age is not a definitive limitation.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
conditioning (psychology), donors, hematologic neoplasms, hematopoietic stem cell transplantation, older adult, cyclosporine, graft-versus-host disease, graft-versus-host disease, acute, influenza, follow-up

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
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