Tuesday, November 06, 2007
Stem cell transplant - a lifelong committment
Some people think I am against transplants. Not at all, I regularly attend a ward round at the biggest transplant center in Britain. There are certainly situations where I recommend it unequivocally. I just want people to be realistic about the likely outcomes.
Everyone is aware that there is a certain mortality to stem cell transplants (SCT), especially in CLL, where at one time we were talking about a 40% risk of death in the first 100 days. Since the introduction or reduced intensity conditioning (RIC) that has been reduced so that in the best centers more than 80% are alive at a year post transplant. It is what happens afterwards that I want to write about today. In next week's Blood an article by Bhatia et al deals with the late consequences of SCT. Th is a report from very reputable centers including City of Hope, University of Minnesota, Ann Arbor, Michican and St Jude's, Memphis.
The paper deals with the long term consequences of transplants in leukemia and lymphoma excluding CLL and these were full intensity transplants not RICs.
By June 30, 2003, 21.6% (n = 320) of the patients who had undergone SCT between 1974 and 1998, and survived at least 2 years, had died. Median age at death was 33.4 years. Most of the deaths (69%) occurred in the 2- to 5-year period after allogeneic SCT, although 43 deaths (13%) did occur after 10 years from SCT.
The graph shows a survival curve comparing patients who had survived for 2 years after SCT with the normal US population of the same age.
For CLL patients it is important to realise that this is a young population. For most of the time covered by the study, the upper age for transplants was 40. CLL patients are generally older, and mostly would have RIC SCT. CLL patients have a more damaged immune system than other leukemic patients and would be more susceptible to infection.
Overall, premature death occurred 10 times more often than expected both in males (8-fold) and females (13-fold). Relative mortality was elevated across all age groups, but was highest in subjects undergoing SCT when younger than 18 years (17-fold). Relative mortality was highest in the 2- to 5-year period after allogeneic SCT (78-fold), and declined dramatically in the 6- to 10-year period (8-fold). Relative mortality remained elevated (2-fold above that of the general population) in patients followed for more than 15 years after SCT.
Two hundred forty-one deaths were observed in patients who had survived disease free for 2 years after SCT. Relapse of primary disease was the leading cause of death(29% of all deaths) mostly between the second and fifth year of follow-up. Chronic graft-versus host disease (cGVHD) was the second most common cause of late mortality accounting for 22% of deaths, while late infection in the absence of cGVHD was the cause of 11% of deaths. Late mortality was attributed to treatment-related causes in (25%), including 7% due to subsequent malignancy, 5% due to pulmonary complications, 3% due to cardiac toxicity, and 8.4% due to miscellaneous treatment-related complications.
The risk of late mortality due to any cause was 2.6-fold increased among individuals older than 45 years at the time of SCT, compared with those who were younger than 18 years; 2.3-fold increased among patients with cGVHD compared with those without cGVHD; and 1.7-fold increased among patients at high risk of relapse at the time of SCT, compared with those at standard risk. Patients undergoing SCT after 1980 were less likely to suffer from relapse-related mortality, compared with those who underwent transplantation before 1980.
In order to look at morbidity the investigators produced a questionnaire which looked at whether the patient had married or stayed married, was employment or not, could obtain health insurance and life insurance, and compared them with their siblings who had mot had a transplant.
Marital rate (proportion currently married) for the survivors was significantly lower compared with siblings (55% vs 69%, P < .001).
SCT survivors were 14-fold more likely to report a health problem preventing them from holding a job compared with siblings (19% vs 2%). Presence of cGVHD (OR = 3.2; 95% CI, 1.9-5.4), and female sex (OR-1.7; 95% CI, 1.1-2.7) were associated with difficulty in holding a job.
SCT survivors were 7-fold more likely to report difficulty in obtaining or retaining health insurance (26% vs 5%, P < .001), and low annual household income (< $20 000) was associated with difficulty in obtaining health insurance (OR = 2.7; 95% CI, 1.4-5.0). However, 90% of the survivors did report health insurance coverage at the time of study participation, although the rate in siblings was 95% (p = 0.01).
A significantly greater proportion of SCT survivors reported difficulty in obtaining or retaining life insurance compared with siblings (30% vs 5%, P < .001) and the survivors were 10-fold more likely to report difficulty in obtaining or retaining life health insurance. Only 56% of the survivors had life insurance at study participation, compared with 76% of the siblings (P < .001).
Tough though it is to have a transplant, it is better than being dead. When it is appropriate a transplant is the right course to take, but it should not be entered into unadvisedly.