Myeloablative Versus Nonmyeloablative Hemopoietic Cell Transplantation (HCT) for Patients with Myelodysplasia (MDS) or AML with Multilineage Dysplasia Following MDS (tAML).
Authors: Scott Bart L. , Maris Michael , Sandmaier Brenda , Storer Barry , Chauncey Thomas , Maloney David G. , Sorror Mohamed , Storb Rainer , Deeg H. Joachim 
Published: April 2020

The median age at diagnosis of MDS is 72 years (yrs), and conventional HCT is not an option for many patients (pts). The primary benefit of nonmyeloablative conditioning regimens is a reduction in acute post-HCT morbidity and mortality. However, this benefit may be offset by an increase in post-HCT relapse. To address these issues, we performed a retrospective review of data from 172 pts over age 40 yrs with a diagnosis of MDS or tAML as determined by WHO criteria who underwent HCT between January 1998 and December 2003. Data were analyzed as of July 28, 2004. One hundred thirty two pts were conditioned with a myeloablative regimen of targeted (800–900 ng/ml) busulfan (starting dose 1mg/kg every 6 hours for 16 doses) and cyclophosphamide (120mg/kg) with or without thymoglobulin. Forty pts selected for a nonmyeloablative regimen because of age or comorbid illnesses were conditioned with 2 Gy TBI with or without fludarabine, 30mg/m2/day for three days. The median age was 52 (40–65) yrs for the myeloablative group, and 62 (40–73) yrs for the nonmyeloablative group. The majority of pts in the nonmyeloablative group had progressed to tAML (55%) and had high risk disease by IPSS (55%). The WHO distribution (highest at any time) was as follows: myeloablative/nonmyeloablative- 34%/55% with tAML, 29%/22% with refractory anemia with excess blasts (RAEB-1/2), and 37%/22% with refractory anemia with or without ringed sideroblasts (RA/RARS). The IPSS distribution (highest at any time) was as follows: myeloablative/nonmyeloablative-26%/55% high, 23%/30% int-2, 41%/15% int-1, and 11%/0% low risk. All pts received HCT from HLA-matched related (50% of myeloablative, 65% of nonmyeloablative) or unrelated donors. There were no differences between the two groups with regards to gender distribution, donor CMV status, recipient CMV status, duration of disease prior to HCT, primary or secondary etiology of MDS, or source of stem cells. Overall survival (OS) [46%/31%], relapse free survival (RFS) [40%/28%], and non-relapse mortality [37%/37%] did not differ significantly between myeloablative/nonmyeloablative pts. There was a trend towards improved RFS in pts with RA/RARS (p=0.16) who received myeloablative HCT, and a trend towards improved RFS in pts with tAML who received nonmyeloablative HCT (p=0.14). Among pts with more advanced disease (RAEB-1/2 or tAML) given myeloablative/nonmyeloablative HCT there were 39%/87% who received induction chemotherapy (IC) pre-HCT and 59%/85% given IC achieved a CR. Post-HCT OS and RFS were similar for pts who achieved CR following IC regardless of conditioning regimen used. Thus, while there was a trend towards superior survival with myeloablative HCT in pts with RA/RARS and with nonmyeloablative HCT in pts with tAML, in this retrospective review there were no significant differences between results obtained with myeloablative and nonmyeloablative conditioning regimens. Furthermore, even though most nonmyeloablative pts had high risk disease, there was no significant difference in RFS between the two groups suggesting that a graft vs. tumor effect was more important than conditioning intensity in preventing relapse in pts with high risk MDS or tAML in CR after IC. This raises the question of whether nonmyeloablative HCT should be considered in all pts with high risk MDS or tAML who achieve a CR with IC.