Treatment of leukemic relapse following unrelated umbilical cord blood transplantation with interleukin-2: potential for augmenting graft-versus-leukemia and graft-versus-host effects with cytokines

Abstract

Summary:In comparison to bone marrow, umbilical cord blood has decreased intrinsic immune responsiveness allowing transplantation across HLA barriers with lower rates of graft-versus-host disease. However, laboratory models have also suggested that cord blood may be extremely sensitive to stimulation by cytokines. We report an adult recipient of an ex vivo expanded, HLA-mismatched, unrelated cord blood transplant who experienced a late extramedullary relapse while still in hematologic remission. Despite demonstrating immune tolerance on minimal immunosuppressive agents, a brief course of intravenous interleukin-2 resulted in rapid, aggressive graft-versus-host and graft-versus-leukemia reactions. This case highlights the potential of cytokine immunomodulation following cord blood transplantation, but also suggests caution in stimulating these cells. Bone Marrow Transplantation (2000) 26, 353-355.

Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies

“…Despite its theoretical advantages over bone marrow transplantation (BMT) from unrelated donors, 16 the lower number of hematopoietic stem cells in CB compared with bone marrow, together with preliminary data showing the importance of cell dose for the outcome of CBT, 1,2 have been of major concern in adult patients. At present, it is almost impossible to evaluate the potential role of UD-CBT in adults.…”

“…First, information about the results of UD-CBT in adults is only available through reports from registries 1-3 (2 of them comprising mainly children 1,2 ), a joint study from 5 U.S. centers reported in abstract form, 4 small study series from single institutions [5][6][7][8][9] (reported mostly only in abstract form 5,6,8 ), or as anecdotal case reports. [10][11][12][13][14][15][16] Secondly, in all but one instance 9 the populations of patients and the conditioning regimens have been heterogeneous. The present series included only adult patients who received the same conditioning (except one case) and who were managed uniformly in terms of prophylaxis and treatment of GVHD as well as with respect to anti-infection and transfusion policy.…”

“…At present, information on the results of UD-CBT in adults comes only from 2 heterogeneous series of patients with different diseases from registries including mainly pediatric cases, 1,2 from 2 heterogeneous series of adult patients recently reported by Eurocord 3 and by 5 U.S. centers, 4 from several small series of adults from a single institution, [5][6][7][8][9] and from anecdotal case reports. [10][11][12][13][14][15][16] This deficit is due mainly to grave concerns about the possibility of graft failure following UD-CBT in adults. 17 None of the series of UD-CBT in adults have used a unique preparative and graft-versus-host disease (GVHD) regimen.…”

Unrelated donor umbilical cord blood transplantation in adults

“…14 Anecdotal case reports of UD-UCBT and small series comprising less than 10 patients have not been taken into consideration. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] To comprehend the extraordinary increase in UD-UCBT activity in recent years, we should note that, as of December 1997, a review of reports in the literature 31 collected data from only 43 recipients of UD-UCBT, of whom only four were adults. In fact, the first report of UD-UCBT in an adult patient with chronic myelogenous leukemia was published in 1996.…”

Treatment of relapsed myelodysplastic syndrome following double umbilical cord blood transplantation with interferon alpha and 5‐azacytidine

“…Such agents have included interleukin-2 (Goldberg et al, 2000;Laws et al, 2000), recombinant human granulocyte-macrophage colony-stimulating factor treatment (Worth et al, 2002), and interferon alpha (IFNa) (Bogdanic et al, 1998;Laws et al, 2000;Arima et al, 2011), often in combination with low dose chemotherapy. To date, the diseases reported to respond to this approach have included chronic myeloid leukaemia, lymphoproliferative diseases, congenital leukaemia and de novo acute myeloblastic leukaemia.…”