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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-02-0506.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3108-3114
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
The toxicity and efficacy of donor lymphocyte infusions given
after reduced-intensity conditioning allogeneic stem cell
transplantation
David I. Marks,
Richard Lush,
Jamie Cavenagh,
Donald W. Milligan,
Steven Schey,
Anne Parker,
Fiona J. Clark,
Linda Hunt,
John Yin,
Steven Fuller,
Elisabeth Vandenberghe,
Judith Marsh,
Timothy Littlewood,
Graeme M. Smith,
Dominic Culligan,
Ann Hunter,
Rajesh Chopra,
Andrew Davies,
Keiren Towlson, and
Catherine D. Williams
From the institutions contributing data to the Clinical
Trials Committee Study and Departments of Haematology at Nottingham
City Hospital, St Bartholomew's and Royal London NHS Trust, Birmingham
Heartlands Hospital, Guy's and St Thomas' NHS Trust, Glasgow Royal
Infirmary, Queen Elizabeth Hospital Birmingham, Manchester Royal
Infirmary, Hammersmith Hospital, Royal Hallamshire Hospital Sheffield,
St George's Hospital London, John Radcliffe Hospital Oxford, Leeds
Blood and Marrow Transplant Centre, Aberdeen Royal Infirmary, Leicester
Royal Infirmary, Christie Hospital Manchester, and British Society of
Bone Marrow Transplantation Registry.
We describe the toxicity and efficacy of donor lymphocyte infusions
(DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations
performed at 16 centers in the United Kingdom. The diseases treated
included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia
(CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9).
Eighty-eight percent received stem cells from sibling donors. The
patients received 130 infusions (median, 1; range, 1-4). Indications
for DLI were unsatisfactory response/disease progression in 51 patients, mixed chimerism in 18, preemptive in 10, and other in 2. Graft hypoplasia was uncommon (11%). Grade II to IV graft-versus-host
disease (GVHD) occurred in 23 of 81 patients (28%) and limited and
extensive chronic GVHD in 5 of 69 and 18 of 69 evaluable patients
(total incidence 33%). Conversion from mixed to full donor chimerism occurred in 19 of 55 evaluable patients (35%) at a median of 48 days
after the DLI; partial responses occurred in 6 patients (total response
rate 45%). Eighteen of 51 (35%) patients with measurable disease
after stem cell transplantation had a complete response (2 molecular),
and 5 a partial response (total response rate 45%). Eleven of 17 evaluable complete responders had full donor chimerism. Eight of 13 patients with follicular NHL had complete responses as did 4 of 12 patients with CML. Clinical and chimeric responses correlated strongly
with acute and chronic GVHD. Forty-seven patients (58%) survive at a
median of 508 days after transplantation (range, 155-1171 days) with a
median Karnofsky score of 90. Thirty-four patients (42%) died at a
median of 211 days after transplantation with the major causes being
progressive disease (26%) and GVHD (9%). Further systematic studies
are required to determine the efficacy and optimum use of DLI for
patients with each disease treated by nonmyeloablative stem cell transplantation.
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