Download İ NSAN KORİYONİK GONADOTROPİNLE (HCG) GVHH DA

İNSAN KORİYONİK GONADOTROPİNLE (HCG) GVHH DA
İMMUNE TOLERANS İNDÜKSYONUNA ULAŞILIYOR.
GHVH İÇİN UYGUN BİR TEDAVİ SEÇENEĞİ Mİ?
Ahmet Elmaağaçlı
Asklepios Klinik Hamburg, Germany
B
ackground: Chronic graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic stem cell transplantation and is associated with a substantial
morbidity and mortality. It is a systemic inflammatory disorder that reflects the lack of immune tolerance between donor-derived immune competent
cells and host organs. Human chorionic gonadotropin hormone (hCG) is a natural occurring hormone
during pregnancy secreted by syncytiotrophoblasts
of the placenta. We had previously observed (Koldehoff et al; J Leukoc Biol 2011) that the rejection
of transplanted skin was significantly delayed by
hCG in a mouse skin transplant model and had
also demonstrated that tryptophan-catabolizing
enzyme, indoleamine-2,3-dioxygenase(IDO), interleukin-10 (IL 10) and T-regulatory cells (Tregs)
increased significantly in females treated with hCG
as preconditioning therapy for in-vitro-fertilization.
Since all these factors are known to induce tolerance and given the low rate of adverse effects, we
off-label used low dose of hCG to treat 20 patients
as forth- or fifth-line therapy with steroid-refractory or intolerant severe-grade chronic GVHD
Results: The median number of sites of chronic
GVHD involvement per patient was 3 (range, 1-6).
hCG therapy was started as 4 or 5th line-therapy
together with preexisting medication with prednisone and a calcineurin inhibitor. Twelve of 20
patients (60%) had an objective partial response
during 8 weeks of hCG treatment with at least
50% improvement according to the TSS score.
Responses included softened skin and subcutaneous tissue; decreased erythema and extent of
sclerodermatous, hidebound skin; improved joint
mobility and gait; gastrointestinal improvements;
and resolution of neuropathy. Nine patients had
stable disease (6 with minor responses). Only one
patient with previous ATG treatment showed progression of her liver GVHD (histologically proven)
and died from GHVD. All other patients were well
and alive. Daily low-dose hCG was well tolerated. Adverse events that were possibly related to
hCG included reversible and asymptomatic CTCAE
grade 4 hypertriglyceridemia (n=1), grade 2 constitutional symptoms (fever, malaise, fatigue; flush,
breast enlargement). IDO expression increased up
to 8 times and IL10-serum level up to 2 times after
3 weeks of hCG therapy (p<0.003 and p<0.04).
Patients: Because all of these factors are known
to induce tolerance and given the low rate of
adverse effects in preconditioning therapy, we
off-label used low dose of hCG (187 IU) to treat
8 male and 12 female patients (median age 48, r.
28-68) with moderate or severe grade of chronic
GVHD according to the NIH criteria; all patients
had been informed of the experimental state of this
treatment and provided written consent.
T-regulatory cell expansion was documented in
3 patients.
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Conclusion: This successful use of hCG in
an immune disorder warrants further studies to
assess its role as an immunosuppressant in GVHD
and potentially other autoimmune disorders.
8. ULUSAL KEMİK İLİĞİ TRANSPLANTASYONU ve KÖK HÜCRE TEDAVİLERİ KONGRESİ