- IGH-DOSE chemoradiotherapy followed by bone marrow transplantation (BMT) with cells from genotypically or phenotypically matched donors has become the treatment of choice for chronic myeloid leukemia (CML), for patients with acute leukemia who have already relapsed or who are at high risk to relapse, and for those with primary resistant di~ease.’.~ The advantage of BMT over conventional chemotherapy lies in the combined effects of the higher myeloablative dose of chemoradiotherapy given pretransplant and the ability of immunocompetent allogeneic donor T lymphocytes to react to residual tumor cells of host origin, ie, the graft-versus-leukemia (GVL) effect!”’ The possibility that allogeneic BMT eliminates leukemia through immune-mediated GVL effects has been suggested ever since the earliest days of e~perimental~”~ and clinical BMT.4” Recent data from murine models imply that GVL effects may also be induced by posttransplant administration of graded increments of immunocompetent allogeneic lymphocytesI6-” and may be additionally increased by in vivo activation of lymphocytes with recombinant human interleukin-2 (rhIL-2).’6-2” Preliminary data from pilot clinical trials suggest that a similar rationale for the treatment and prevention of relap~e’”~’ may be applicable. The present report documents the first successful induction of GVL effects by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL) in a patient with resistant acute lymphoblastic leukemia (ALL) who relapsed shortly after BMT. Similar cases with a variety of malignant hematologic diseases have been successfully treated at many BMT centers, including our own. The cumulative international data indicate that cell therapy using major histocompatibility complex (MHC)-matched allogeneic lymphocytes should be considered the treatment of choice for persistent disease or relapse post-BMT. Moreover, our data show that patients with tumor cells resistant to allo-CT can still respond to in vivo 2 in vitro activation of donor PBL by rhIL-2. H with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhlL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhlL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo-ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistant minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT. 0 1996 by The American Society of Hematology.