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Mixed chimaerism is common at the time of acute graft‐versus‐host disease and disease response in patients receiving non‐myeloablative conditioning and allogeneic stem cell transplantation
Author(s) -
Mattsson Jonas,
Uzunel Mehmet,
Brune Mats,
Hentschke Patrik,
Barkholt Lisbeth,
Stierner Ulrika,
Aschan Johan,
Ringdén Olle
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.03174.x
Subject(s) - medicine , transplantation , fludarabine , cyclophosphamide , gastroenterology , stem cell , total body irradiation , busulfan , immunology , hematopoietic stem cell transplantation , surgery , chemotherapy , biology , genetics
We report the clinical outcome and results of chimaerism analysis in various cell lineages of 30 patients given non‐myeloablative conditioning, followed by allogeneic stem cell transplantation (SCT). The commonest diagnoses were chronic myelogenous leukaemia ( n = 11) and solid tumours ( n = 11). Twenty‐one patients received SCT from human leucocyte antigen (HLA)‐identical siblings and nine from matched unrelated donors. Median patient age was 53 (28–77) years. Four non‐myeloablative protocols were used, including fludarabine (30 mg/m 2 × 3–6), busulphan (4 mg/kg × 2), cyclophosphamide (Cy) (30 mg/kg/day × 2) or total body irradiation (2 Gy), and anti‐thymocyte globulin. The patients were analysed by polymerase chain reaction (PCR) analysis of minisatellites on days 14, 21 and 28, then every other week up to 3 months and monthly thereafter. All samples were cell separated for T, B and myeloid cells using immunomagnetic beads. Eighteen patients were alive at a median follow‐up of 11 (6–20) months. Acute graft‐versus‐host disease (GVHD) occurred in 22 patients. Eighteen of the 22 patients with acute GVHD showed mixed chimaerism (MC) in the T‐cell fraction at the time of acute GVHD. However, all patients with acute GVHD showed donor chimaerism (DC) in the T‐cell fraction median 76 (7–414) days after onset versus three out of eight patients without acute GVHD, P < 0·001]. Disease response was diagnosed in 15 patients, median 100 (37–531) days after SCT. At the time of disease response, six out of15 patients showed MC in the T‐cell fraction. In conclusion, mixed chimaerism in the T‐cell fraction is common at the time of acute GVHD and disease response in patients conditioned with non‐myeloablative therapy.