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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2419-2425
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
In vivo CAMPATH-1H prevents graft-versus-host disease following
nonmyeloablative stem cell transplantation
Panagiotis D. Kottaridis,
Donald W. Milligan,
Rajesh Chopra,
Ronjon K. Chakraverty,
Suparno Chakrabarti,
Stephen Robinson,
Karl Peggs,
Stephanie Verfuerth,
Ruth Pettengell,
Judith C. W. Marsh,
Stephen Schey,
Premini Mahendra,
Gareth J. Morgan,
Geoff Hale,
Herman Waldmann,
M. Carmen Ruiz de Elvira,
Catherine D. Williams,
Stephen Devereux,
David C. Linch,
Anthony H. Goldstone, and
Stephen Mackinnon
From the Departments of Hematology, University College
London Hospital, London, England; Heartlands Hospital, Birmingham,
England; Christie Hospital, Manchester, England; St George's Hospital,
London, England; Guy's Hospital, London, England; Queen Elizabeth
Hospital, Birmingham, England; Leeds General Infirmary, Leeds, England,
and Therapeutic Antibody Centre, University of Oxford, Oxford,
England.
A novel nonmyeloablative conditioning regimen was investigated in
44 patients with hematologic malignancies. The median patient age was
41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning
consisted of CAMPATH-1H, 20 mg/day on days  8 to 4; fludarabine, 30 mg/m2 on days 7 to 3; and melphalan, 140 mg/m2 on day 2. Thirty-six recipients received
unmanipulated granculocyte colony-stimulating factor-mobilized
peripheral blood stem cells from HLA-identical siblings, and 8 received
unmanipulated marrow from matched unrelated donors. GVHD prophylaxis
was with cyclosporine A alone for 38 patients and cyclosporine A plus
methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable
patients had sustained engraftment. Results of chimerism analysis using
microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were
mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete
remission or with no evidence of disease progression. Seven patients
relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were
no cases of grades III-IV acute GVHD. Only 2 patients developed grade
II acute GVHD, and only 1 had chronic GVHD. The estimated probability
of nonrelapse mortality was 11%. Although longer follow-up is needed
to establish the long-term remission rates, this study demonstrates
that this nonmyeloablative preparative regimen is associated with
durable engraftment, minimal toxicity, and low incidence of GVHD.
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