Long-Term Outcomes of Patients with Advanced Mantle Cell Lymphoma Treated with Allogeneic Hematopoietic Cell Transplantation after Nonmyeloablative Conditioning

Previous studies have shown that a subset of patients with relapsed Mantle cell lymphoma (MCL) benefit from nonmyeloablative allogeneic hematopoietic stem cell transplant (HCT), but literature is lacking regarding their long-term outcomes. We examined long term-survivals, resolution of chronic graft-versus-host-disease, and predictive factors in a large group of patients with MCL.

Seventy MCL patients, age 32 to 75 yrs, were conditioned with 2 Gy TBI alone or combined with fludarabine +/- rituximab followed by HCT from related (n=35) or unrelated (n=35) donors. Table 1 summarizes patient and transplant-related characteristics.  Proportional hazards models were used to estimate the hazards of relapse or mortality after adjustment for known risk variables.

After a median follow-up of 7.1 (0.2- 12.8) yrs, 34 patients were alive, 30 in continued remission and 4 after salvage therapies given for progression (n=1) or relapse (n=3).  The 5-yr incidence of non-relapse mortality (NRM) for all 70 patients was 28%. The 5-yr rate of relapse was 26%, while those of overall (OS) and disease-free survival (DFS) were 55% and 46%, respectively. (Figure 1).  Among 33 pts with sufficient follow-up, 10-yr NRM, relapse, OS and DFS rates were 41%, 18%, 44% and 41%, respectively.

Eighty % of surviving patients were off immunosuppression at last follow-up, with a median time to cessation of 35 (range 1-95) months. Among the 34 surviving patients, the median Karnofsky performance status at last contact was 90%.

Relapsed/refractory disease at time of HCT predicted a higher rate of relapse (HR 2.94, P=0.05) but not OS at 5 (51% versus 58%, p=0.29) or 10-yrs (43% versus 45%, p=0.89).  High-risk CMV status predicted inferior OS (HR 2.32 P=0.02) and DFS (HR 2.22 P=0.03). Low CD3 dose (HR 2.04 P=0.05) predicted DFS.

We conclude that some MCL patients given nonmyeloablative allogeneic HCT may achieve long-term survival and come off IS, despite having relapsed or refractory disease at the time of HCT. Future studies addressing appropriate timing of allogeneic HCT versus non-HCT therapies for patients with MCL are needed

 

.  TABLE 1: Patient Characteristics
	Median	Range
Age (years)	57	32-75
	N	%
Sex
F	17	24
M	53	76
Conditioning Regimen
2 Gy TBI	4	6
2 Gy TBI + Auto	4	6
2 Gy TBI + Flu 30 mg/mē x 3	55	79
2 Gy TBI + Flu 30 mg/mē x 3 + Rituxan	5	7
2 Gy TBI + Rituxan	2	3
Donor type
HLA Matched Related	33	47
HLA Matched Unrelated	29	41
HLA 1 Antigen mismatched	8	11
GVHD prophylaxis
Cyclosporine/MMF	49	70
Cyclosporine/MMF/Rapamycin	2	3
Tacrolimus/MMF	15	21
Tacrolimus/MMF/Rapamycin	4	6
HCTCI
0	12	17
1- 2	26	37
> 3	30	43
Number of prior regimens
1 - 2	15	21
3 - 4	27	39
5 - 6	16	23
>7	12	17
Previous autologous transplant
Failed	28	40
Tandem  auto/allo	7	10
No	35	50
Disease status at HCT
CR	26	37
PR	19	27
Relapsed/Refractory	25	36
Bulky lymphadenopathy (5 cm or >)
Y	12	17
N	58	83
CMV risk
High	38	54
Intermediate	8	11
Low	24	34

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1: Cumulative incidences of (A) NRM and relapse (B) OS and DFS.