Abstract

We previously reported 2-year overall survival (OS) of 60% among 64 pts given nonmyeloablative HCT (

Sorror et al,
JCO
2005
,
23
:
3819
). Here, we update our results on the initial 64 pts with median follow up of 5 (range:3–7) years and report on 18 additional pts with emphasis on: 1) long-term disease control, 2) resolution of chronic GVHD, and 3) outcomes of pts with poor-risk genomic features. Conditioning consisted of 2 Gy total body irradiation with or without fludarabine (90 mg/m2). Median age was 56 (range 42–72) years and median number of prior regimens was 4. Eighty-seven percent, 56%, and 41% of pts had fludarabine-refractory CLL, chemo-resistant disease at HCT, and unfavorable cytogenetics, respectively. Donors were related (n=52) or unrelated (n=30). The incidences of grades II, III, and IV acute GVHD were 39%, 14%, and 2% respectively, and chronic extensive GVHD was 51%. Overall disease response was seen in 70% of pts, and 55% achieved complete remission (CR). Estimated 5-years rates of non-relapse mortality (NRM), progression/relapse, OS, and progression-free survival (PFS) were 23%, 38%, 50%, and 39%, respectively (Table 1 shows outcomes by donor type). Overall, 42 patients are alive; 31 in CR, 4 in PR, 1 with stable disease, and 6 with relapse/progression. Among 14 responding pts tested and found to have molecular eradication of their disease, 2 died of NRM, 2 eventually relapsed, and 10 remained negative at a median of 6 years. Lymph node diameter >5 cm was an independent risk factor for relapse (p=0.008) and PFS (p=0.01), while unfavorable cytogenetics (Table 2) were not (p=0.65 and 0.88, respectively). Among the pts who were alive at 5-years, 76% were without chronic GVHD while 24% received immunosuppression for chronic GVHD. Median performance status (PS) was 100% and 90% among pts without or with chronic GVHD, respectively. Nonmyeloablative HCT resulted in a median survival of 5 years for fludarabine-refractory CLL. Sustained molecular remissions and continuing resolution of chronic GVHD with good PS were observed in most pts with extended follow up. Nonmyeloablative HCT might change the natural history of CLL with unfavorable cytogenetics if considered earlier.

Table 1:

Outcomes by donor type

Donor
At 5-yearsRelated (n=52)Unrelated (n=30)p-value
  
CR 48 67 0.04 
NRM 22 24 0.97 
Pgrossion/relapse 43 26 0.18 
PFS 35 51 0.28 
OS 49 51 0.57 
Pts alive with chronic GVHD requiring immunosuppression 14  
Donor
At 5-yearsRelated (n=52)Unrelated (n=30)p-value
  
CR 48 67 0.04 
NRM 22 24 0.97 
Pgrossion/relapse 43 26 0.18 
PFS 35 51 0.28 
OS 49 51 0.57 
Pts alive with chronic GVHD requiring immunosuppression 14  
Table 2:

Outcomes of pts with poor genomic features

Abnormality (n)Pts alivePts who died
Median interval, yearsMedian interval, years
CR/PR/PDFrom DxFrom HCTCR/PR/NE/PDFrom DxFrom HCT
PR indicates partial remission; PD, progression; Dx, diagnosis; and NE, not evaluated 
del 17p (7) 4/0/0 6.5 3.3 1/0/0/2 6.5 0.3 
del 11q (7) 1/2/2 8.1 2.1 1/0/0/1 7.5 0.7 
Tri 12 (7) 4/0/0 6.7 4.4 0/0/2/1 3.8 0.2 
Complex (9) 4/0/0 11.4 5.7 0/1/0/4 10.5 3.5 
Abnormality (n)Pts alivePts who died
Median interval, yearsMedian interval, years
CR/PR/PDFrom DxFrom HCTCR/PR/NE/PDFrom DxFrom HCT
PR indicates partial remission; PD, progression; Dx, diagnosis; and NE, not evaluated 
del 17p (7) 4/0/0 6.5 3.3 1/0/0/2 6.5 0.3 
del 11q (7) 1/2/2 8.1 2.1 1/0/0/1 7.5 0.7 
Tri 12 (7) 4/0/0 6.7 4.4 0/0/2/1 3.8 0.2 
Complex (9) 4/0/0 11.4 5.7 0/1/0/4 10.5 3.5 

Author notes

Disclosure:Off Label Use: Off-label discussion of total body irradiation, fludarabine, cyclosporine, and mycophenolate mofetil.