Increased Leukaemia Free Survival (LFS) in Patients with Cytogenetic High Risk AML after Related or Unrelated Hematopoietic Cell Transplantation (HCT) Compared to Chemotherapy in the OSHO 96 and 2002 Studies.
Authors: Niederwieser Dietger , Becker Cornelia , Krahl Rainer , Al-Ali Haifa-Kathrin , Heyn Simone , Cross Michael , Lange Thoralf , Gerhardt Anke , Schulze Antje , Haehling Detleff , Schulze Manfred , Freund Matthias , Kettner Erika , Dölken Gottfried , Assmann Michael , Wolf Hans-Heinrich , Zschuppe Ernst , Peter Norma , Franke Astrid , Wedding Ulrich , Uharek Lutz , Kreibich Ute , Grobe Norbert , Ittel Thomas , Florschuetz Axel , Opitz Bernd , Senftleben Karin , Schirmer Veronika , Fiedler Friedrich , Huhn Renate , Helbig Werner 
Published: October 2019

Cytogenetic high risk AML (abn 3q26, abn 11q23, −5/5q-, −7/7q- and complex) has a dismal prognosis with a two year overall survival (OS) below 20% even in young patients. Attempts to improve survival by intensifying consolidation chemotherapy have so far failed. In the two OSHO protocols AML 96 and AML 2002, we investigated the role of allogeneic HCT in these patients. A total of 708 patients have been entered into the two studies between 1997 and the present. The first protocol (AML 96) compared two different schedules employing identical total dosages of intermediate AraC and Idarubicin. The second protocol (AML 2002) studied the role of two different induction therapies in patients failing to reach CR after the first induction therapy. In patients with cytogenetic high risk AML, the search for a donor (either familial or, if none available, then unrelated) was initiated as soon as possible. Allogeneic HCT was scheduled either after induction or after first consolidation therapy. HCT was performed after conditioning with cytoxan and 1200 cGy total body irradiation followed by GvH-D prophylaxis with cyclosporine and methotrexate. Of the 708 patients, 138 (19,5%) had high risk cytogenetics and 77 (55,8%) of these went into remission after one or two cycles of induction chemotherapy. Of these 77 patients, 54 were alive and in CR after the first consolidation therapy and were allocated to either related (n=12) or unrelated (n=21) HCT or, if no compatible donor was available, to a two courses of chemotherapy (n=21). Median age of the patients was 36 (range 17–51) years, 46 years (range 23–59) years and 49 (range 16–60) years for patients receiving related HCT, unrelated HCT and chemotherapy respectively. Data were analysed as intention to treat.LFS at 3 years was 67 ± 14% after related and 44 ± 14 % after unrelated HCT, but decreased to 11 ± 7% in patients receiving chemotherapy. Allogeneic HCT results were significantly better than the results of chemotherapy with p-values of 0.005 and 0.002 for related vs. chemotherapy and unrelated vs. chemotherapy respectively. Major differences in relapse incidences were seen between the three groups, with the lowest RI at 3 years after related HCT 26±0.13%, followed by unrelated HCT 48±15% and by chemotherapy 89±8% (p=0.003 and p=0,0006 for chemotherapy vs. related or unrelated HCT). Transplant related mortality at 3 years was 10±9%, 14±10% and 6±6% for patients receiving HCT from related donors, from unrelated donors and chemotherapy, respectively.

Conclusions: From the results observed in the two prospective, multicenter studies we conclude that consolidation with allogeneic HCT is superior to chemotherapy in younger patients with high risk cytogenetics. While no differences in TRM were seen between the three treatment arms, a lower relapse incidence after related and unrelated HCT contributed to the improved OS.