Myeloablative Treosulfan as Preparative Regimen for Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Centre Experience.

Treosulfan (TREO), a water-soluble bifunctional alkylating agent, has demonstrated strong immunosuppressive and antileukemic activity as well as profound stem cell toxicity in animal studies. Due to the advantageous clinical toxicity profile lacking significant non-hematologic organ toxicities, high-dose TREO in combination with cyclophosphamide (CY) has recently been evaluated in patients (pts) with an increased risk for organ toxicities precluding standard myeloablative conditioning regimens before allogeneic stem cell transplantation (SCT). Between 8/00 and 10/03, we treated 52 patients (pts) not eligible for conventional therapy with TREO in order to reduce toxicity in a myeloablative setting. Diagnoses were AML (n=14), ALL (n=11), MM (n=8), NHL (n=7), MDS (n=5), CML (n=4) and aplastic syndromes (n=3). 18 patients were grafted in early disease (1st or 2nd complete remission, chronic phase, or incipient first relapse (BM blasts < 10%). The remaining pts were classified as having advanced disease. Donors were identical siblings (n=24), non-identical family members (n=l), matched unrelated (n=14) or mismatched unrelated (n=13) donors. Conditioning regimen consisted of TREO 36g/qm (n=19) or 42g/qm (n=28) and CY 120mg/kg BW, 5 pts received TREO 42g/qm and fludarabine 150mg/qm. GvHD prophylaxis consisted of CSA alone (n=l) or in combination with short course MTX (n=25), alemtuzumab (n=22) or ATG (n=4). ANC > 500/μl and platelets > 20000/μl were reached at day 15 and 16 respectively. Acute GvHD grade II - IV occurred in 31% of pts and chronic GvHD in 60% of pts. Overall (OS) and disease free survival (DFS) were closely related to disease status. OS and DFS was 93% and 82,9% after a median of 18 months (range 0,9–38,5 months) for pts with early disease. In advanced disease the OS was 57,4% and the DFS 47,9% after a median of 4,8 months (range 0,3 – 22,9 months), respectively. In early disease, a single patient died of invasive aspergillosis associated with grade IV aGvHD. Another patient developed a relapse of CML which was successfully treated with DLI. Clinical relevant adverse events occurred in patients with advanced disease: MOF (n=7), VOD (n=2), infectious problems associated to GvHD grades II – IV (n=4), and pulmonary embolism (n=l). TREO as part of a myeloablative regimen seems to be effective and safe even in pts not eligible for conventional myeloablative therapy.