Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex

Unmanipulated autologous bone marrow transplant (ABMT) offers patients with chronic myelogenous leukemia (CML) a long-term survival of 10%, at best. I mmunotherapy has a role in the myeloid leukemias, and there is increasing e vidence that of all hematopoietic neoplasms, CML may be the most susceptibl e to immune regulation. Roquinimex is known to enhance T cell, NK cell and macrophage activity. A phase II study was initiated in March 1992 to evalua te the role of roquinimex in Ph chromosome-positive CML post ABMT, Patients were conditioned with busulfan/cyclophosphamide followed by reinfusion of unmanipulated Ph-positive bone marrow stem cells (>1 x 10(8) NBC/kg), When engraftment of neutrophils (ANC) reached 100/mu l, patients received oral r oquinimex twice weekly, escalating to a maximal dose of 0.2 mg/kg in 2 week s. Seventeen patients have entered the study; 11 in first chronic phase (CP 1); two in second chronic phase (CP2) and four in accelerated phase (AP), A ll required significant myelosuppressive therapy prior to ABMT to maintain stable blood counts and most had also received prior interferon therapy. Al l patients survived the transplant. Subsequent toxicity consisted mainly of musculoskeletal aches and peripheral edema. Additionally, specific skin ch anges were observed including graft-versus-host-like disease and eccrine sw eat gland necrosis, Eight out of 17 patients are alive 28-60 months post AB MT, Of the nine patients who died, two were in CP2 and three in AP, All pat ients in CP1 went into a complete hematological remission post ABMT and sev en of the 11 patients had at least a major cytogenetic response (greater th an 65% Ph-negative metaphases) at 1 year or beyond and four of the 11 patie nts had a complete cytogenetic response at 2 years or beyond. Cytogenetic r esponse post transplant often developed over time and did not simply repres ent post ABMT engraftment with Ph-negative cells. The clinical and cytogene tic data in these patients are encouraging and suggest that roquinimex may have significant activity when given post ABMT to patients with Ph-positive CML.