ORIGINAL ARTICLE
Long-term outcome after allo-SCT: close follow-up on a large cohort
treated with myeloablative regimens
YR Abou-Mourad
1,2
, BC Lau
2
, MJ Barnett
1,2
, DL Forrest
1,2
, DE Hogge
1,2
, SH Nantel
1,2
, TJ Nevill
1,2
,
JD Shepherd
1,2
, CA Smith
1,2
, KW Song
1,2
, HJ Sutherland
1,2
, CL Toze
1,2
and JC Lavoie
1,2
1
Leukemia/Bone Marrow Transplant Program of British Columbia, British Columbia Cancer Agency, Vancouver General Hospital,
Vancouver, British Columbia, Canada and
2
Department of Medicine, University of British Columbia, Vancouver, British Columbia,
Canada
We analyzed the late outcomes of 429 long-term survivors
post allogeneic hematopoietic SCT (allo-HSCT) who
received transplant in our center between 1981 and 2002,
and were free of their primary disease for X2 years after
allo-HSCT. Late recurrent primary malignancy was
found in 58 (13.5%) patients and was the primary cause
of late death. A total of 37 (8.6%) patients died of non-
relapse causes at a median of 5.5 years (range, 2–15.6
years) post allo-HSCT. The major non-relapse causes of
death were chronic GVHD (cGVHD), secondary malig-
nancy and infection. The probabilities of OS and EFS
were 85% (95% cumulative incidence (CI) (81–89%)) and
79% (95% CI (74–83%)) at 10 years, respectively.
Long-term allo-HSCT survivors were evaluated for late
complications (median follow-up, 8.6 years (range, 2.3–
22.8 years)). cGVHD was diagnosed in 196 (53.1%)
survivors. The endocrine and metabolic complications
were hypogonadism in 134 (36.3%) patients, osteopenia/
osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%),
hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%).
Hypertension was diagnosed in 79 (21.4%), renal impair-
ment in 70 (19.0%), depression in 40 (10.8%) and sexual
dysfunction in 33 (8.9%) survivors. We conclude that in
patients who receive allo-HSCT as treatment for hema-
tological malignancy and who are free of their original
disease 2 years post transplant, mortality is low and the
probability of durable remission is high. Lifelong surveil-
lance is recommended.
Bone Marrow Transplantation (2010) 45, 295–302;
doi:10.1038/bmt.2009.128; published online 13 July 2009
Keywords: late complications; long-term survivors;
allogeneic hematopoietic stem cell transplantation
Introduction
Allogeneic hematopoietic SCT (allo-HSCT) is currently an
established treatment modality for a variety of hematological
and non-hematological malignancies, and for some non-
malignant life-threatening diseases.
1–4
The annual number of
allo-HSCT procedures as well as the number of diseases for
which allo-HSCT is considered appropriate, have expanded
over the years.
5
Survival post allo-HSCT has also gradually
improved with development of technological aspects in
supportive care, enhanced histocompatibility testing, safer
conditioning regimens, more effective GVHD prophylaxis
and better management of opportunistic infections. As
currently more patients survive the early post allo-HSCT
period and remain free of their primary disease for several
years, the potential long-term complications are more
evident. For many allo-HSCT survivors, cure or control of
the underlying disease is not accompanied by full restoration
of physical and psychological health.
6–10
Most of the studies
reported on long-term survivors are multi-center registry-
based reviews.
8,11–13
In our center, more than a thousand
allotransplants have been performed over the last two
decades, with a close follow-up of survivors annually or bi-
annually. Our large single institution cohort gives us a
unique opportunity for reviewing long-term outcomes.
To determine the late outcomes and long-term complica-
tions of survivors after allo-HSCT, we retrospectively
studied the charts of 429 patients who were alive and free
of their original disease for at least 2 years post-
transplantation. We hereby report our results focusing on
the medical problems seen in long-term survivors and stress
the need of medical surveillance.
Patients and methods
Patient population
Between January 1981 and December 2002, a total of 894
patients underwent allo-HSCT for hematological malig-
nancies at Leukemia/BMT Program of British Columbia
in Vancouver, Canada. All patients provided a written
informed consent. A total of 465 patients died or had
relapsed within 2 years of transplantation and were
Received 16 September 2008; revised 30 March 2009; accepted 13 April
2009; published online 13 July 2009
Correspondence: Dr YR Abou-Mourad, Department of Medicine,
Division of Hematology, BC Cancer Agency, Gordon & Leslie Diamond
Health Care Center, Room 10149, 10th Floor, 2775 Laurel Street,
Vancouver, British Columbia, Canada V5Z 1M9.
E-mail: ymourad@bccancer.bc.ca
Bone Marrow Transplantation (2010) 45, 295–302
& 2010 Macmillan Publishers Limited All rights reserved 0268-3369/10 $32.00
www.nature.com/bmt

excluded from this analysis. A total of 429 patients were
alive and free of their primary disease for at least 2 years
after transplantation and represented the population of this
retrospective analysis. The Institutional Review Boards of
the Vancouver General Hospital, and the University of
British Columbia approved this retrospective analysis. The
patients and transplant characteristics for the entire group
are summarized in Table 1.
Data collection
Most survivors were still being seen annually or bi-annually
by their primary BMT physician. A total of 291 long-term
survivors (79%) were seen regularly and had a date of last
follow-up at our clinics o2 years before the data were
pulled. A total of 78 patients (21%) had a date of last
follow-up of 2–3 years, but communications, letters, study
results and clinic notes were regularly received by their
primary BMT physician from their primary oncologist/
hematologist or family physician. Pertinent information
regarding patients is regularly prospectively entered in our
program database (BMT Serve 3.1.4) whenever new
information is available. Determination of remission status,
cause of death and monitoring for the occurrence of late
complications were performed by computer database
search and by reviewing charts, clinic notes, medical
correspondence, study results, death certificates and au-
topsy information, when available.
Statistical analysis and definitions
The date of allo-HSCT was considered day 0, and follow-
up date was to the date of last medical examination.
Survival analyses were done according to the method of
Kaplan and Meier
14
and compared using the log-rank test.
OS was calculated from the date of allo-HSCT to the date
of death from any cause or until the date of last known
follow-up. PFS was calculated from the date of allo-HSCT
to the date of death or to the date of relapse of primary
disease. Patients who died while in relapse were considered
to have relapse-related death, even if this was not the
recorded proximal cause of death. Similarly, patients who
died with active chronic GVHD (cGVHD) were considered
to have died of this complication even if other complica-
tions were recorded as the proximal cause of death.
Infection was considered the cause of death among patients
dying of infection without active cGVHD or relapse. Long-
term survivors are patients who are still alive with or
without relapse at last follow-up. Late complications are
defined as complications occurring in long-term survivors.
Clinical grading of cGVHD was based on Seattle criteria.
15
Arterial hypertension was defined as chronically elevated
systolic blood pressure X140mmHg and/or a diastolic
pressureX90mmHg. Dyslipidemia was defined as elevated
fasting lipid profile above normal range, and renal
impairment was considered when serum creatinine was
persistently above the upper limit of normal. In men,
hypogonadism was defined as serum testosterone levels
below normal range with the need for testosterone
replacement therapy. In women, hypogonadism was
defined as premature onset of menopausal symptoms
coupled with high leutinizing hormone and follicle stimu-
lating hormone levels. Bone mineral density was measured
by dual energy X-ray absorptiometry. Bone mineral density
within 1to2.5 s.d. of mean young adult values defined
osteopenia; whereas osteoporosis was present when bone
mineral density values were greater than 2.5 s.d. below
the mean young adult values.
The competing risk method was used to calculate the
cumulative incidence (CI) of relapse, non-relapse mortality
and secondary malignancy. The following were evaluated
as potential prognostic factors for relapse and survival: age,
sex, initial diagnosis, interval from diagnosis to HSCT, type
and subtype of HSCT, donor–recipient sex, conditioning
regimen, GVHD prophylaxis and cGVHD. Univariate and
multivariate analyses were performed using a Cox propor-
tional hazard technique.
16
Results
A total of 429 allo-HSCT recipients were alive and free of
their primary disease for at least 2 years after transplantation
Table 1 Characteristics of the patient population and transplant
details
No. of patients 429
Age (years) median (range) at HSCT 39 (14–57)
Male gender 233 (54.3%)
Primary diagnosis
Chronic myeloid leukemia 117 (27.2%)
AML 112 (26.1%)
Non-Hodgkin’s lymphoma 53 (12.3%)
Myelodysplastic syndrome/myelofibrosis 40 (9.3%)
Multiple myeloma 39 (9.1%)
ALL 34 (7.9%)
Severe aplastic anemia/PNH 17 (4.0%)
Chronic lymphocytic leukemia 10 (2.3%)
Others 7 (1.6%)
Time (months) from diagnosis to HSCT
median (range)
4.9 (0.3–181)
Donor–recipient relationship and histocompatibility
Identical twin 8 (1.8%)
HLA-identical sibling 309 (72.0%)
HLA-mismatched sibling 19 (4.4%)
HLA-matched unrelated donor 76 (17.7%)
HLA-mismatched unrelated donor 17 (3.9%)
Source of stem cells
BM 392 (91.4%)
Peripheral blood 33 (7.7%)
BM+peripheral blood 4 (0.9%)
Conditioning regimen
a
TBI-based regimen 193 (45%)
Bu/Cy
±
other agent(s) 227 (52.9%)
Others (chemotherapy-only) 9 (2.1%)
GVHD prophylaxis
CsA+MTX±other drug(s) 378 (88.1%)
CsA
±
other drug(s) 29 (6.8%)
MTX
±
other drug(s) 8 (1.8%)
T-cell depletion
±
other drug(s) 6 (1.4%)
No prophylaxis 8 (1.8%)
Abbreviations: Bu¼busulfan; CsA¼ cyclosporine A; Cy¼ cyclophospha-
mide; MTX¼methotrexate; PNH¼ paroxysmal nocturnal hemoglobin-
uria; TBI¼ total body irradiation.
a
Only one patient had non-myeloablative transplant.
Late complications, survivors, allogeneic transplantation
YR Abou-Mourad et al
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Bone Marrow Transplantation