Graft-versus-leukemia-induced complete remission following unrelated umbilical cord blood transplantation for acute leukemia

Abstract

Summary:A 15-year-old female received an unrelated three of six HLA antigen matched umbilical cord blood (UCB) transplant for refractory, relapsed T-cell ALL. Conditioning consisted of TBI, melphalan, and anti-thymocyte globulin (ATG), with cyclosporin A (CsA) and solumedrol for GVHD prophylaxis. She engrafted and a day 34 bone marrow aspirate showed 100% donor cells and no evidence of leukemia. The post-transplant course was complicated by mild grade I acute GVHD involving skin, and limited chronic GVHD of the gut which resolved with the addition of 1 mg/kg/day of steroids to her CsA prophylaxis. One hundred and ninety days after transplantation the patient developed pancytopenia and was subsequently found to have a leukemic relapse. Immunosuppression was discontinued and she was started on G-CSF and erythropoietin. Moderate skin and gut GVHD developed which was treated with both topical and low-dose oral steroids. Over the next few weeks she became transfusion independent and a follow-up bone marrow aspirate showed complete remission. She continued in complete remission for 4 months, at which time localized leukemic relapse was found in a soft tissue breast mass in spite of continued bone marrow remission. from BMT but lack a suitably matched conventional transplant donor.1-4 Preliminary results have suggested that UCB transplantation may be associated with a lower incidence of acute GVHD than unrelated bone marrow, and require less stringent HLA matching.2-4 While less GVHD is a potential benefit of UCB transplantation, there is concern that UCB may not be able to generate a sufficient GVL effect in patients with hematologic malignancies, resulting in increased relapse rates and limiting its practical utility. In this report we describe a patient who relapsed after undergoing UCB transplantation from a partially mismatched (3/6) unrelated donor for refractory relapsed T cell ALL. A complete remission was achieved following discontinuation of immunosuppression and institution of cytokine support. Whether UCB cells generate a GVL effect in all patients is unknown, but this case report clearly demonstrates that UCB has the potential to generate a GVL effect and this effect can be powerful enough to induce a complete remission. As the biology and mechanisms of GVHD and GVL are more completely understood, it may become possible to uncouple these two immune responses and maximize the benefits of hematopoietic stem cell transplantation without compromising anti-leukemic effects. Case reportA 15-year-old white female had been diagnosed with CD7 +

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

“…From the present clinical experience it is clear that, despite the decreased incidence and severity of GvHD associated with UCB grafts, GvL immunologic effects are maintained [34]. Clinical reports of allogeneic UCB recipients have not identified increased relapse rates [7][8][9]14,15].…”

Umbilical cord blood transplantation: Where do we stand?

“…Another indirect observation suggesting the presence of GVT activity after UCB transplantation is highlighted by a patient with acute lymphoblastic leukemia who suffered a relapse after transplantation but reentered complete remission after withdrawal of immunosuppression [81]. It is also notable that in one study, only 4 (8%) of 48 patients with CML suffered relapse after UCB transplantation [25].…”

“…Because donor leukocytes are not available after UCB transplantation from unrelated donors, alternative strategies for augmenting GVT and antiviral activity should be considered. Suggested approaches include IL-2 augmentation of natural killer cell-mediated cytotoxicity, ex vivo expansion and activation of UCB T-cells, and employment of dendritic cell vaccines designed to stimulate the immune response against neoplastic cells [93][94][95][96].…”

Induction of graft-versus-host disease and a graft-versus-leukemia effect using ubenimex in a patient with infantile leukemia relapsing after an unrelated cord blood transplant

“…1,2 Howrey et al 8 reported that discontinuation of CYA, and G-CSF administration generate a GVL effect, which can be powerful enough to induce complete remission in patients who relapse after UCBT. Immunotherapy is not always durable, and relapse continues to occur very late.…”