Adoptive Immunotherapy in the Treatment of Post-Transplant Relapse and Epstein-Barr Virus Lymphoproliferative Disorders
Adoptive immunotherapy has recently been recognized as an effective treatment for both post-transplant relapse of chronic myelogenous leukemia (CML) and the treatment of post-transplant Epstein-Barr Virus lymphoproliferative disorders (EBV-LPD). Sixteen patients have received donor-derived leukocytes containing a dose of CD3+ cells ranging between 0.2–1.0 × 106 CD3+ cells/kg for treatment of EBV-LPD. Fifteen of the sixteen patients re-sponded with complete eradication of lym-phoma. Eight of thirteen evaluable patients developed either acute and/or chronic graft-vs.-host disease (GvHD). Of these eight, six exhibited mild GvHD and two pa-tients developed extensive chronic GvHD. Nine of the sixteen patients are alive and well approximately 6–50 months post-treat-ment. No patient has had recurrence of lymphoma.
Donor leukocyte infusions have also been effective in the treatment of post-transplant relapse of chronic myelogenous leukemia. We have utilized a dose escalation approach attempting to achieve a graft-vs.-leukemia effect without a graft-vs.-host re-action in patients with hematologic, cytogenetic, or molecular relapse of CML following T cell depleted transplants. Thirty-six patients have been treated with escalating doses of donor leukocytes ranging from 1 × 105−5 × 108 CD3+ cells/kg. Of these patients with hematologic (chronic phase or accelerated phase), cytogenetic, and/or molecular disease, thirty-two have responded. GvHD was seen in eleven of the responding pa-tients and none of the four nonresponders. Of the eleven patients developing GvHD, five developed limited chronic GvHD and six developed extensive GvHD. The dose of T cells required to achieve a response correlated with the status of disease at the time of the donor leukocyte infusion. In addition, the development of GvHD correlated with the cumulative dose of T cells administered. Dose escalations of donor derived lymphocytes result in durable remissions following post-transplant relapse of CML. Patients re-quiring a smaller dose of donor leukocytes to achieve remissions had a lower incidence of GvHD complicating this therapy.
KeywordsToxicity Lymphoma Leukemia Pneumonia Penicillin
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- 5.Porter EL et al. (1994) Induction of graft-versushost disease as immunotherapy for relapsed chronic myelogenous leukemia. NEJM 330: 100–106Google Scholar
- 11.Antin JH et al. (1991) Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies. Blood 37: 2139Google Scholar
- 12.Shapiro RS et al. (1988) Treatment of B cell lymphoproliferative disorders with interferon alpha and intravenous gamma globulin. NEJM 318: 1334Google Scholar
- 17.Bonini C et al. (1994) Transfer of the HSV-TK gene into donor peripheral blood lymphocytes for in vivo immunomodulation of donor antitumor immunity after Allo-BMT. Blood 84 (1): 110aGoogle Scholar