Molecular remission of chronic myeloid leukaemia following a non‐myeloablative allogeneic peripheral blood stem cell transplant: in vivo and in vitro evidence for a graft‐versus‐leukaemia effect

Abstract

Summary. Two patients with chronic myeloid leukaemia (CML) received a non-myeloablative preparative regimen of cyclophosphamide and¯udarabine, followed by an unmanipulated, G-CSF-mobilized, peripheral blood stem cell transplant from an HLA-identical sibling. Chimaerism, evaluated in myeloid and T-lymphoid lineages by PCR of minisatellite variable regions, showed day 14 post-transplant haemopoietic recovery to be 90% autologous in both patients. On day 30 the bone marrow showed only 1/20 and 2/18 donor metaphases. By day 100 post transplant both had 100% donor myeloid and lymphoid lineages as assessed by karyotype and minisatellite chimaerism analysis. They subsequently became RT-PCR negative for BCR-ABL. Both survive 7 and 14 months post transplant in molecular remission of CML. In one, donor T cells, stimulated with pre-transplant CML cells, induced 30±50% inhibition of pre-transplant leukaemic CFU-GM, but did not inhibit CFU-GM in the day 60 marrow (46% Ph-negative recipient, 54% donor). These results show that a non-myeloablative allotransplant can induce molecular remissions of CML through a graft-versusleukaemia effect.

Long-term follow-up of a randomized trial comparing the combination of cyclophosphamide with total body irradiation or busulfan as conditioning regimen for patients receiving HLA-identical marrow grafts for acute myeloblastic leukemia in first complete remission

“…Indeed, a recent encouraging report of nonmyeloablative preparative regimens in CML supports this hypothesis. 5 The third trial reporting a different conclusion from ours may not be comparable, as only 51 such patients with AML in CR1 were randomized. 3 A retrospective registry analysis from European Blood and Marrow Transplant group (EBMT) also failed to find a difference between BUCY and CYTBI.…”

“…[2][3][4] We do agree that intensification of induction treatment has improved outcome in children with AML. 5 Analysis of patient groups in the Berlin-Frankfurt-Münster study (AML-BFM 93) (n ϭ 471) comparable with those of the CCG trial (children with…”

The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia

“…[8][9][10][11][12][13][14] In all, 10 patients had sustained donor engraftment. T-cell engraftment was more rapid than myeloid engraftment, with all 12 patients having X90% donor T-cell chimerism by day þ 30.…”

“…[6][7][8][9]10 We previously reported the characteristics of a low-intensity preparative SCT regimen, which does not myeloablate the recipient and has low toxicity. [11][12][13] We used this transplant protocol to treat a series of CML patients who had a matched sibling donor. The aim of the study was to determine whether a reduced intensity transplant regimen could achieve a durable molecular remission in CML by a GVL effect, while reducing TRM.…”

Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients

“…DLI also induces GVT and reduces mixed chimerism. 26 Several observations can justify allogeneic transplantation in solid tumors: (1) there is no risk of reinfusing autologous malignant cells; (2) graft-versus-malignancy effects can target tissue-specific polymorphic antigens which are not derived from a hematopoietic lineage; and (3) some solid tumors are sensitive to immunotherapy, such as renal carcinoma, melanoma and (with less evidence) ovarian cancer. Some reports have already demonstrated evidence of a GVT effect in renal carcinoma and in breast cancer.…”