H e m a t o lo g y E d u c a t io n - European Hematology Association

16 th Congress of the European Hematology Association
the first reports likely described relapse of the original
leukemia because the “donor” origin of the leukemia
was based on classic cytogenetics of leukemic cells in a
transplant setting with donor/recipient sex-mismatch,
in which the cell origin was demonstrated on sex chromosome.
However, today it is recognized that loss of
the Y chromosome and duplication of the X chromosome
does occur in leukemic cells. Thus nowadays,
only molecular proof of the donor origin can only be
accepted using PCR of VNTRs as the most widely used
tool. Using these stringent criteria, leukemias or malignancies
of donor cell origin, although rare, do exist. 50 A
further complexity came also recently from a study by
the Seattle group showing that malignancies could also
be transmitted through the graft either at a premalignant
stage or as a minimal clone undetectable before
transplantation. 51
Lymphomas and post-transplant lymphoproliferative disorders
Patterns of post-transplant lymphoproliferative disorders
(PTLD) have been recently assessed among 26,901
patients who underwent allogeneic HSCT. PTLD developed
in 127 recipients, with 105 (83%) cases occurring
within 1 year post-transplant. In multivariate analyses,
PTLD risks were strongly associated with T-cell depletion
of the donor marrow, ATG use, and unrelated or
HLA mismatched grafts. Significant associations were
also confirmed for acute and chronic GVHD. The
increased risk associated with unrelated or HLA mismatched
donors was limited to patients with T-cell
depletion or ATG use. 52
Today, prospective monitoring of EBV activation and
early treatment intervention with Rituximab has dramatically
changed these features. While risk factors may
remain the same, the true incidence of EBV-reactivation
and evolution to overt PTLDs remain essentially
unknown. Furthermore, the potent iatrogenic consequence
in term of infection due to long-lasting
Rituximab-induced B-cell lymphopenia warrants further
studies. Late-onset B-cell neoplasm and Hodgkin’s disease
have been described but remain exceptional. 53
Solid tumors
Several studies 32,54–62 have reported that survivors of
HSCT have an increased risk of developing new solid
cancers with the risk rising among long-term survivors
from 2% to 6% at 10 years after transplantation. Several
factors contributed to this increase, including total body
irradiation TBI, which has been a mainstay of the
preparative regimens for allogeneic HCT until recently,
primary disease, male sex, and pre-transplantation therapy.
However, with longer follow-up, solid tumors after
Busulfan cyclophosphamide have been recently reported
(especially lung cancers). 2,63 Chronic GHVD and
immunosuppressive therapy have also been shown to
contribute to excess risk, particularly for squamous cell
carcinomas of the buccal cavity and the skin. 58 Young
age at transplantation has been reported to be a strong
risk factor in some, but not all, previous studies.
The largest studies today included multi-institutional
cohort of 28,874 allogeneic transplant recipients with
189 solid malignancies. Overall, patients developed new
solid cancers at twice the rate expected based on general
population rates (observed-to-expected ratio 2.1; 95%
confidence interval 1.8–2.5), with the risk increasing
over time; the risk reached three-fold among patients
followed for 15 years or more after transplantation.
New findings showed that the risk of developing a nonsquamous
cell carcinoma following conditioning radiation
was highly dependent on age at exposure. Among
patients irradiated at ages under 30 years, the relative
risk of non-squamous cell carcinoma was nine times
that of non irradiated patients, while the comparable
risk for older patients was 1.1. Chronic GVHD disease
and male sex were the main determinants for risk of
squamous cell carcinoma. 64
However, even in this largest cohort the very longterm
survivors are still few and some solid tumor type
might be under-estimated. This is especially true for
breast carcinomas that tend to develop very late after
transplantation. The EBMT and the Seattle group thus
sought to determine the risk among 3337 female 5-year
survivors who underwent an allogeneic transplantation.
59 Fifty-two survivors developed breast cancer at a
median of 12.5 years following HSCT. Twenty-fiveyear
cumulative incidence was 11.0%, higher among
survivors who received TBI (17%) than those who did
not receive TBI (3%). Hazard for death associated with
breast cancer was 2.5.
Altogether, these data indicate that allogeneic transplant
survivors face increased risks of solid cancers, supporting
strategies to promote lifelong surveillance
among these patients.
Quality of life, sexuality, and social integration
There are many studies available on the quality of life
after HSCT but results are rather heterogeneous. 65–68
Quality of life is generally perceived as satisfactory to
good in the majority of patients after HSCT. Whereas
some studies support the observation that with time
quality of life continues to improve others do not. Some
patients with more advanced disease report better quality
of life after transplant than patients with less
advanced disease. While quality of life is subjective and
reflects the patient view, health status is assessed by the
physician. One of the major drivers of health status is
chronic GVHD, and this observation may or may not be
concordant with the patient’s view. 43,69 Coping strategies
of some patients with late complications, such as chronic
GVHD, may provide them with the ability of perceiving
quality of life as much better than their treating
physician. 69,70
Chronic fatigue in otherwise asymptomatic patients
is a common complain after allogeneic and autologous
HSCT. There is a great diversity in the prevalence
reported, which may reflect sample heterogeneity, time
of assessment since HSCT, type of treatment and population
at risk. Behavioral interventions, as for instance,
individually tailored aerobic exercises, are associated
with sustained improvement of severe fatigue.
Several studies have addressed the issue of sexuality
after HSCT and have in general found that libido was
diminished, more so in women. 71 Sexual dysfunction
may be the consequence of hormonal abnormalities,
genital problems, and psychological stress. Some of
these dysfunctions may be corrected by hormonal sub-
| 346 | Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1)