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Indian Journal of Human Genetics
Medknow Publications on behalf of Indian Society of Human Genetics
ISSN: 0971-6866 EISSN: 1998-362x
Vol. 10, Num. 2, 2004, pp. 76-77
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Indian Journal of Human Genetics, Vol. 10, No. 2, July-December, 2004, pp. 76-77
Case Report
HLA Chimerism in allogenic haplo-identical peripheral blood stem cell transplant
Chhaya Sonal U., Sawant Rajesh B., Rajadhyaksha Sunil B.
Department of Transfusion Medicine, Tata Memorial Hospital, Parel, Mumbai - 400012
Correspondence Address: Department of Transfusion Medicine, Tata Memorial Hospital, Parel, Mumbai - 400012,
sonalu@rediffmail.com
Code Number: hg04017
ABSTRACT
HLA antigens were used as markers to establish the presence of chimerism
(i.e. simultaneous presence of two lymphocyte populations from recipient
as well as donor) in a patient with chronic granulomatous disease treated
with one haplotype matched stem cell transplant. Neutrophil engraftment
occurred on Day 6 post peripheral blood stem cell transplant (PBSCT). Platelet
counts were maintained above 20x109/L. Six months after the allogenic
PBSCT, lymphocyte population was chimeric and cells of both donor (father)
and host HLA type were present. The patient revealed a shift in his HLA
antigen profile and there was evidence of donor cell engraftment. The HLA
phenotype A26,CwXX,B8,DRB1*03//A32,Cw4,B35,DRB1*16// represented his true
phenotype whereas A11,Cw7,B62,DRB1*14 represented donor (father) origin..
HLA system as a genetic marker is a useful additional approach to determine
engraftment following an allogenic haplo-identical stem cell transplantation.
Keywords: HLA, Chimerism, PBSCT
INTRODUCTION
It has been recognized that determining the degree to which donor′s lymphohematopoietic system has either superceded or come into equilibrium with the host can be critical to establishing the success of a hematopoietic stem cell transplant (HSCT).[1],[2] Mixed chimerism refers to the coexistence of lymphohematopoietic cells of both donor and recipient within a given cellular compartment in the recipient′s circulation. We present here the presence of chimerism (two lymphocyte populations) using the HLA system in a haplo-identical peripheral blood stem cell transplant (PBSCT).
Clinical History
A 2 year old male patient with CGD received PBSCT from his haploidentical father. T- cell depletion of the stem cell product, to reduce GVHD was performed using 1 mg (in 1 ml) of purified OKT3 IgG (Ortho Pharmaceuticals, Raritan, New Jersey).[3] The patient engrafted without any major complications post PBSCT. Neutrophil engraftment occurred on Day +6 of the PBSCT. Platelet counts were maintained above 20x109/L as a result of non-myeloablative conditioning regimen for the patient. 7 months post PBSCT, the patient received granulocyte transfusion (dose 4x1010 cells) of donor origin for resistant respiratory infection.
Blood Transfusion History
The patient did not receive any blood transfusion before PBSCT. Leukocyte depleted and irradiated packed red cells (16 units) and single donor platelets (2 units) were transfused over a period of six months post PBSCT.
Analysis of Mixed Chimerism
HSC engraftment was analysed by chimeric studies in the recipient at 6 months post PBSCT. HLA typing of the recipient was performed by the standard serological technique for HLA class I[4] and analyses based on sequence specific primers for HLA-DR using polymerase chain reaction.[5]
DISCUSSION
Chimerism is used as a tool for determining complete or partial engraftment in a recipient of HSCT. In non-myeloablative transplants, early patterns of chimerism may predict either GVHD or graft loss. Mixed hematopoietic chimerism following a non myeloablative HLA mismatched bone marrow transplant has been demonstrated using HLA allele specific monoclonal antibodies by flow cytometric analysis or alternatively by variable number tandem repeats(VNTR). The percentage of donor DNA present in the total white blood cells, CD3+ and CD3- subsets has been estimated by microsatellite analysis (STR).[1],[6]
In CGD, the level of donor chimerism is associated with the presence of oxidase positive neutrophils in recipient′s circulation.[7] We assessed chimerism 6 months post transplant using the HLA system. Peripheral blood lymphocytes of the recipient were of a mixed nature. The patient revealed a shift in his HLA antigen profile. There was evidence of transient presence of recipient HLA alleles followed by the appearance of engrafted HLA mismatched alleles
[Figure - 1].
We therefore propose that HLA typing can be performed for assessment of donor engraftment wherever facilities for flowcytometry or VNTR/STR are unavailable. Detection of donor HLA antigens is a simple, reproducible, useful additional approach to determine engraftment following an allogenic haplo-identical PBSCT. Periodic monitoring of the recipient HLA antigen profile to assess levels of chimerism may also be used to successfully guide methods to manipulate donor immune reconstitution to enhance a GVL effect.
REFERENCES
| 1. | Sykes M, Preffer F, McAfee S, Saidmain SL, Weymouth D, Andrews DM, et al. Mixed lymphohaematopoietic chimerism and graft versus - lymphoma effects after non-myeloablative therapy and HLA mismatched bone marrow transplantation. Lancet 1999;353:1755-9. Back to cited text no. 1 |
| 2. | Spitzer TR, McAfee S, Sackstein R, Colby C, Dey B, Saidman S, et al. Mixed lymphohematopoietic chimerism and delayed donor leukocyte infusions following nonmyeloablative conditioning and HLA matched and mismatched donor bone marrow transplantation. In. Immunotherapy and Bone Marrow Transplant Editors Spitzer TR and Mazumdar A, ISBN-0-87-99-36029 Blackwell Publishers; 1995. p. 321-32. Back to cited text no. 2 |
| 3. | Filipovich AH, Ramsay NKC, Warkentin PI, Mcglave PB, Goldstein G, Kersey JH. Pretreatment of donor bone marrow with monoclonal antibody OKT3 for prevention of acute graft versus host disease in allogeneic histocompatible bone marrow transplantation. Lancet 1982;5:1266-9. Back to cited text no. 3 |
| 4. | Terasaki PI, Bernoco D, Park MS, Ozturk G, Iwaki Y. Microdroplet testing for HLA-A, -B, -C and -D antigens. Am J Clin Pathol 1978;69:103-20. Back to cited text no. 4 [PUBMED] |
| 5. | Bunce M, O'Neill CM, Barnado MCNM, Krausa P, Browning MJ, Morris PJ, Welsh KI. Phototyping. Comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 and DQB1 by PCR with 144 primer mixes utilizing sequence specific primers (PCR-SSP). Tissue Antigens 1995;46:355-67. Back to cited text no. 5 |
| 6. | Joseph HA, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T, et al. Establishment of complete and mixed donor chimerism after allogenic lymphohematopoietic transplantation: Recommendations from a workshop at the 2001 tandem meetings. Biol Blood Marrow Transplant 2001;7:473-85. Back to cited text no. 6 |
| 7. | Nagler A, Ackerstein A, Kapelushnik J, Or R, Naparsteck E, Slavin S. Donor lymphocyte I. Post non-myeloablative allogenic BPSCT for CGD. Bone Marrow Transplant 1999;24:339-42. Back to cited text no. 7 |
Copyright 2004 - Indian Journal of Human Genetics
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