Pediatric Allogeneic Bone Marrow and Stem Cell Transplantation in Alberta, Canada † 754

Abstract Analysis of chimerism for the evaluation of engraftment and rejection after allogeneic stem cell transplantation is now standard practice (ASCT). The most common technique used is PCR amplification of short tandem repeats (STRs) and variable number of tandem repeats (VNTRs). Data on informativeness of various VNTRs or STRs in HLA identical recipient donor pairs in a population is essential to establish a scheme of sequential testing. To determine the informativeness in our population, we screened five STRs namely FES, THO 1, VWA, ACTBP2, and F13A1 and 1 VNTR, APOB, in allogeneic bone marrow transplant patients with their HLA identical donors. Samples from 310 patients who underwent haematopoietic stem cell transplantation (HSCT) during the period 1993–2005 were analyzed. All donors were HLA identical siblings or related family members of the patient. Of the 310 patients, 120 (39%) were from southern India, 88 (28%), 25(8%), and 59 (19%) from northern, eastern and western parts of India respectively. Seventeen (5%) patients were from other countries (Maldives (n=4), Oman (n=4), Sri Lanka (n=2), Singapore (n=1), Mauritius (n=1), Pakistan (n=3), Bhutan (n=2)). For 15 (5%) of these 310 patients only amelogenin PCR results were available. The other 295(95%) patients and donors were studied by PCR for one or more of the polymorphic repeat sequences, (STRs or VNTR) namely FES, THO 1, VWA, ACTBP2, F13A1 and APOB. Of all the six markers used THO1 was the most informative (55%) and F13A1 the least (20%). Informativeness of the markers THO1+VWF, THO1+VWF+ACTBP2, THO1+VWF+ACTBP2+FES was 79, 87, and 92 percent respectively. By combining one, two or three markers, we could discriminate between 68 to 92 percent of the patient donor pairs. Addition of marker APOB to this panel discriminated 95% of the HLA identical patient donor pairs. Usage of Genescan analysis in practice to evaluate chimerism status has improved the utility of these markers from 95% to 97%. Using a combination of all these markers along with a polymorphic marker in the b-globin gene and Y chromosome specific amelogenin marker, we were able to discriminate 99% of the patient donor pairs. We have established an algorithm for evaluating chimerism in the Indian population using molecular markers in 310 patients and their HLA identical related donors. This data may be useful for transplant centers in adopting a strategy for evaluating chimerism following HLA identical ASCT.

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Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Patients with UDCA-Resistant Primary Biliary Cirrhosis

Stem Cells and Development ◽

10.1089/scd.2013.0500 ◽

2014 ◽

Vol 23 (20) ◽

pp. 2482-2489 ◽

Cited By ~ 36

Author(s):

Li Wang ◽

Qin Han ◽

Hua Chen ◽

Ke Wang ◽

Guang-liang Shan ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Primary Biliary Cirrhosis ◽

Mesenchymal Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Bone Marrow ◽

Biliary Cirrhosis ◽

Allogeneic Bone ◽

Mesenchymal Stem Cell Transplantation

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IL-22 Is Critical To The Pathogenesis Of Cutaneous Gvhd Mediated By Th17 Cells

Blood ◽

10.1182/blood.v122.21.4482.4482 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4482-4482

Author(s):

Hemamalini Bommiasamy ◽

Laura Ott ◽

Shelly West ◽

LeShara M Fulton ◽

Angela Panoskaltsis-Mortari ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Stem Cell ◽

Mouse Model ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Th17 Cells ◽

Acute Gvhd ◽

Allogeneic Bone ◽

Congenital Diseases

Background Allogeneic hematopoietic stem cell transplantation is used to treat a number of acquired and congenital diseases; however, a major complication of this therapy is graft versus host disease (GvHD). GvHD is a severe inflammatory disease caused by donor T cells recognizing host organs as foreign and mounting an immune response against them. Current treatment for GvHD is an immunosuppressive drug regimen that can predispose patients to opportunistic infections. Therefore, it is of critical importance to further understand the underlying mechanisms that mediate GvHD pathogenesis in efforts to develop novel therapeutic treatments. Previous work from our lab demonstrated that TH17 cells mediate severe cutaneous GvHD and that inhibiting IL-17 activity using a neutralizing anti-IL17 antibody was protective in a mouse model of skin GvHD. TH17 cells also produce the cytokine IL-22, which is known to be involved in skin inflammation resulting from psoriasis. We tested whether IL-22 from TH17 cells is also pathogenic in a mouse model of GvHD in which ex vivo polarized TH17 cells from B6 mice are transferred to lethally irradiated allogeneic B6D2 mice. Method B6D2 recipient mice were lethally irradiated with 900 cGy from a Cesium source. The following day recipient mice were given 3 x 106 T cell depleted bone marrow cells supplemented with 3-4 x 106 Th17 cells that had been polarized in vitro from fluorescence activated cell sorted CD4+/CD62Lhi T cells that had been cultured as described previously (Carlson et al Blood 2009). Recipient mice were followed for survival and scored for clinical GVHD using a standard scoring system. Additionally, recipient mice were evaluated clinically for cutaneous GVHD and scored for tissue pathology. GVHD organs were evaluated for the production of pro-inflammatory cytokines by ELISA and qPCR. Treated animals received control IgG or anti-IL-22 antibody (16mg/kg) weekly for four weeks starting on the day of transplant (Day 0). Results We found substantial expression of IL-22 mRNA in the skin of recipient mice who were transplanted with donor Th17 cells compared to those receiving naïve T cells alone (p< 0.05). When we evaluated the function of IL-22 produced by Th17 cells, we found a statistically significant decrease in cutaneous GVHD induced by Th17 cells in recipient animals treated with anti-IL-22 mAb (p< 0.05). While there was a decrease in cutaneous GVHD in the mice treated with anti-IL-22 mAb, there was no difference in overall survival or induction of GVHD outside of the cutaneous compartment. Additionally, we found increased expression of mRNA for IL-22 from a cohort of patients with late acute GVHD after allogeneic stem cell transplantation. Conclusions Unlike in the GI tract, the generation of IL-22 appears to play a pro-inflammatory role in the manifestation of cutaneous GVHD in mice after allogeneic bone marrow transplantation. High levels of mRNA for IL-22 were also found in the skin from a cohort of patients with late acute GVHD. These data suggest that targeting IL-22 may be beneficial in the treatment of cutaneous GVHD. Disclosures: Fouser: Pfizer: Employment.

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