الفهرس 
Hematopoietic stem cell Transplantation
Diffuse large B cell lymphomaOnly 14 pages are availabe for public view
 |  | from | 268 |  |  |
| | | from | 268 | | |
Abstract
Over the past 40 years, bone marrow and hematopoietic
stem cell transplantation have been used with increasing
frequency to treat numerous malignant and nonmalignant
diseases.
Although; marked improvements in survival rate
following allogeneic HSCT was achieved, graft versus host
disease (GVHD) remains the major cause of morbidity and
mortality associated with allogeneic transplantation and
stands as a significant barrier to this therapy.
Graft versus host disease (GVHD) is an immune driven
disorder where donor T cells react and proliferate in response
to host antigens leading to an immune reaction that can affect
several target organs including liver, skin, and the
gastrointestinal tract. Rates of GVHD vary from (30-40%) in
transplant from related donors to (60-80%) in transplant from
unrelated donors.
Some reports have been done discussing the role of
adenosine-tri phosphate (ATP) as an endogenous dangerous
signal evoking systemic inflammatory response enhancing
GVHD and affecting tumor growth and spread.Recent murine studies using CD73-deficient mice have
shown that CD73-generated adenosine can be manipulated to
influence both the severity of GVHD and the strength of the
GVL effect.
A prospective study was held at Ain Shams University
BMT unit with recruitment of 30 donors as control and30
patients who were eligible for allo-HSCT for diverse benign
and malignant hematological disorders. All of these patients
had fully matched donors except for one patient who
received haplotype transplants from her mother.
Of these patients, 19 were males (63.3%) and 11 were
females (36.7%). Their age ranged from 16-55 years old,
whereas 22 donors (73.3%) were males and 8 were females
(26.7%) and their age ranged from 16-65 years old.
Enrolled cases have different diagnosis including: 13
cases with AML, six cases with ALL, six patients had
aplastic anemia, two patients had MDS, another two patients
diagnosed with NHL, and finally the last case had CML.
All of the cases were subjected to routine pre-transplant
history taking, thorough clinical examination and different
investigations as complete blood picture, liver profile, kidney function test, bone marrow aspiration, trephine,
flowcytometry, cytogenetic study, and viral markers.
Assessment of CD73 positive cells via flowcytometry
on peripheral blood samples in donors and in recipients were
done before conditioning and once GVHD occurs (within 6
months) with assessment of severity of GVHD via clinical
examination, and other investigations as needed.
Patients were subjected to variable conditioning
protocols according to diagnoses. Candidates were followed
up for 6 months post-transplant for disease recurrence,
complications with different investigations ordered on
demand.
Acute GVHD, affected six patients (20%) with two of
them (33.3%) with grade III and another two (33.3%) with
severe grade IV aGVHD.
On the other hand, cGVHD affected 10 patients
(33.3%). six patients (20%) had chronic hepatic GVHD. Four
patients (13.3%) had chronic cutaneous GVHD, 3 patients
(10%) had pulmonary cGVHD, while chronic gut GVHD had
occurred in 2cases (6.7%).Secondary graft failure affected only two patients
(7.4%), whereas no cases of primary graft failure were
reported in our study.
Bacterial infections nearly affected the majority of
studied population (25 patients= 83.3%), 20 patients (66.7%)
had viral infection mostly CMV, and 17 ceases (56.7%) had
fungal infections with only two of them (6.7%) had severe
mucormycosis.
Assessment of plasma level of CD73 in both recipients
and donors were done and showed higher levels in recipients
either pre-transplant (m=58.24 ±19.68) or at time of GVHD
(m=65.78 ±19.03) compared to donors (m=29.08 ±14.14).
Correlation of plasma level of CD73 in recipients with
incidence of post-transplant complications showed that its
pre-transplant levels in recipients was correlated with chronic
GVHD and mortality rate with statistical significance (pvalue
0.004, 0.013 respectively), while it didn’t show any
correlation with either aGVHD or relapse (p-value 0.270,
0.988 respectively).
Pre-transplant CD73 level in recipients showed a
negative correlation of significance with aGVHD grading (P –value 0.0499) while it was statistically insignificant with
severity of cGVHD (p-value 0.658).
As regard role of CD73 in prediction of post-transplant
complications, recipients’ CD73 levels were a good predictor
of cGVHD with sensitivity of 100% and specificity of 65% at
levels ≤61.07%, also it could predict mortality with a sensitivity
of 92.9% and specificity of 75% at levels >57.67%.
While in donors, CD73 had a good predictive value with
sensitivity of 100% and specificity of 78.6% at levels ≤26.86%,
as well CD73 at level >27.14% could predict mortality with a
sensitivity of 85.7% and specificity of 62.5%.
So, finally we conclude that CD73 expression in
recipients was an independent predictor of cGVHD, while it’s
expression in both recipients and donors were an independent
predictor of mortality.