Abstract 606

Background:

alloHCT is offered with curative intent to patients with hematologic malignancies, and conventionally-computed survival estimates are offered for prognosticating outcomes. However, conventionally-computed survival estimates do not take into account elapsed time (and changing hazards with time survived); conditional survival overcomes these limitations, by calculating the probability of survival after having already survived a certain period of time – such data are unavailable for alloHCT recipients. We describe cause-specific (relapse-, GvHD-, treatment-related) conditional survival after alloHCT, providing clinically relevant information for patients who have survived 6 mos, 1, 2, and 5y after alloHCT.

Methods:

From 1976 to 2006, 2,427 consecutive patients received alloHCT for a hematologic malignancy at a single institution (median age: 34.7y [0.6–72.5]). Vital status and cause of death were determined using National Death Index, Social Security Death Index and medical records.

Results:

As of 12/31/2007, a total of 1413 deaths (58% of the cohort) were observed; 39% attributed to recurrent disease; 34% to GvHD; 12% to infection; 5% to cardiopulmonary disease; 2% to subsequent malignant neoplasm (SMNs); and 8% to other causes. Conventionally-computed probability of survival was 44.6% at 5y and 41.2% at 10y from alloHCT. On the other hand, conditional on survival for 6 mo, 1, 2, and 5y after alloHCT, 5-y survival rates were 62%, 75%, 83%, and 93%, respectively (Figure A). The cohort was at a 40-fold increased risk of any death compared with the general population (95%CI=38.2–42.4); at a 25.6-fold increased risk of death due to pulmonary complications, 3.3-fold risk due to SMNs, and 2.3-fold risk due to cardiovascular complications. Among patients followed for 15+y after HCT, the risk of all-cause mortality was 2.6-fold that of the general population (95%CI=1.8–3.7). Standardized mortality ratios (SMR) and cause-specific conditional mortality rates by primary diagnosis are summarized in the Table.

Individuals who survived the first 5y had negligible (≤5%) risk of relapse- and GvHD-related mortality over the subsequent 5y. Treatment-related mortality increased over time; among those who survived 5y, treatment-related mortality rates exceeded relapse-related mortality (Figure B). After adjustment for demographics, underlying diagnosis and treatment era, individuals with chronic GVHD (cGVHD) had a significantly lower risk of relapse-related mortality (RR=0.43, 95%CI=0.4–0.5) compared to those without cGVHD.

Conclusions:

The projected 5-y survival rates improve conditional on time survived from alloHCT; 5-y survival exceeds 93% for those who have already survived 5y. However, alloHCT recipients who have survived 15+y continue to remain at increased risk of death compared to the general population. cGVHD is associated with decreased risk of relapse-related mortality. Both relapse-related and GvHD-related mortality rates decline with time, such that, among those who have survived 5y, treatment-related mortality exceeds relapse-related mortality. Conditional survival estimates provide clinically relevant prognostic information, helping inform preventive and interventional strategies.

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Table.

Cause-specific mortality in patients undergoing allogeneic HCT

From alloHCT1 yr survivors2 yr survivors5 yr survivors
5-y mortality (%)SMR (95%CI)5-y mortality (%)SMR (95%CI)5-y mortality (%)SMR (95%CI)5-y mortality (%)SMR (95%CI)
All Patients Relapse 18.6 40.3 (38.2–42.4) 11.9 12.2 (11.1–13.4) 6.5 7.6 (6.7–8.6) 1.4 3.5 (2.9–4.3) 
 GvHD 16.4 8.7 6.6 2.0 
 TRM 11.5 3.3 5.0 2.1 
ALL (n=635) Relapse 25.6 63.9 (57.7–70.0) 18.7 21.1 (17.5–24.8) 12.3 11.8 (9.2–14.8) 1.8 4.0 (2.0–6.0) 
 GvHD 17.3 10.9 7.1 0.8 
 TRM 13.3 3.0 0.9 2.1 
AML (n=749) Relapse 22.5 48.3 (43.9–52.7) 12.8 14.1 (11.7–16.5) 7.0 9.3 (7.4–11.4) 1.1 4.6 (3.3–6.4) 
 GvHD 12.2 9.0 6.9 1.5 
 TRM 12.2 3.4 5.7 2.1 
CML (n=596) Relapse 7.6 22.3 (19.7–24.9) 4.6 7.4 (5.9–8.9) 1.6 4.9 (3.8–6.3) 0.7 2.8 (1.9–3.9) 
 GvHD 18.9 7.7 6.9 2.2 
 TRM 7.3 2.7 3.6 2.4 
NHL (n=235) Relapse 21.4 45.9 (38.2–53.6) 16.9 13.3 (9.1–17.6) 12.6 8.6 (5.6–12.7) 5.0 2.6 (0.9–5.6) 
 GvHD 17.7 6.2 5.6 0 
 TRM 11.0 6.4 3.5 3.3 
MDS (n=212) Relapse 12.5 35.3 (28.8–41.8) 7.1 7.5 (4.4–10.6) 2.1 4.2 (2.3–7.1) 2.0 3.5 (1.5–6.7) 
 GvHD 20.5 8.7 10.7 9.8 
 TRM 16.4 3.1 2.0 0 
From alloHCT1 yr survivors2 yr survivors5 yr survivors
5-y mortality (%)SMR (95%CI)5-y mortality (%)SMR (95%CI)5-y mortality (%)SMR (95%CI)5-y mortality (%)SMR (95%CI)
All Patients Relapse 18.6 40.3 (38.2–42.4) 11.9 12.2 (11.1–13.4) 6.5 7.6 (6.7–8.6) 1.4 3.5 (2.9–4.3) 
 GvHD 16.4 8.7 6.6 2.0 
 TRM 11.5 3.3 5.0 2.1 
ALL (n=635) Relapse 25.6 63.9 (57.7–70.0) 18.7 21.1 (17.5–24.8) 12.3 11.8 (9.2–14.8) 1.8 4.0 (2.0–6.0) 
 GvHD 17.3 10.9 7.1 0.8 
 TRM 13.3 3.0 0.9 2.1 
AML (n=749) Relapse 22.5 48.3 (43.9–52.7) 12.8 14.1 (11.7–16.5) 7.0 9.3 (7.4–11.4) 1.1 4.6 (3.3–6.4) 
 GvHD 12.2 9.0 6.9 1.5 
 TRM 12.2 3.4 5.7 2.1 
CML (n=596) Relapse 7.6 22.3 (19.7–24.9) 4.6 7.4 (5.9–8.9) 1.6 4.9 (3.8–6.3) 0.7 2.8 (1.9–3.9) 
 GvHD 18.9 7.7 6.9 2.2 
 TRM 7.3 2.7 3.6 2.4 
NHL (n=235) Relapse 21.4 45.9 (38.2–53.6) 16.9 13.3 (9.1–17.6) 12.6 8.6 (5.6–12.7) 5.0 2.6 (0.9–5.6) 
 GvHD 17.7 6.2 5.6 0 
 TRM 11.0 6.4 3.5 3.3 
MDS (n=212) Relapse 12.5 35.3 (28.8–41.8) 7.1 7.5 (4.4–10.6) 2.1 4.2 (2.3–7.1) 2.0 3.5 (1.5–6.7) 
 GvHD 20.5 8.7 10.7 9.8 
 TRM 16.4 3.1 2.0 0 

TRM=Treatment related mortality

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
hematologic neoplasms, hematopoietic stem cell transplantation, graft-versus-host disease, graft-versus-host disease, chronic, allogeneic hematopoietic stem cell transplant, cancer, cardiac complications, cor pulmonale, infections, pulmonary complications

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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