Abstract

Introduction

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare form of acute leukemia associated with an overall bad prognosis. Only very few cases have been reported to reach durable remissions thanks to chemotherapy alone. Allogeneic hematopoietic stem cell transplantation (HSCT) using a myelo-ablative conditioning regimen (MAC) has been reported to be the gold standard treatment for BPDCN (Roos-Weil et al, 2013). However, little is known about the place of reduced-intensity/non-myelo-ablative conditioning regimens (RIC/NMA) in this setting.

Methods

We retrospectively collected from the database of the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) all cases of BPDCN treated with allogeneic HSCT. Immunophenotypes at diagnosis were centrally reviewed in order to confirm diagnosis according to the Garnache-Ottou diagnostic criteria (Garnache-Ottou et al, 2009). Twenty-eight patients had a diagnostic score of 2 or more. The remaining 15 patients all had CD4+ CD56+ disease, but as they were mostly diagnosed before publication of this score, other markers (such as CD123, BDCA-2 and BDCA-4) were not performed routinely at that time, precluding calculation of a score at least equal to 2.

Results

From February 2003 to January 2014, 43 patients with BPDCN received an allogeneic HSCT in 21 French centers. PatientsÕ characteristics are summarized in table 1. Median age was 57 (range: 20-72), sex ratio (M/F) was 2.1/1 and most patients were in CR1 at time of transplant. Sibling transplantation was performed in 42% of cases. Peripheral blood was the main source of stem cell used in this study (70% of cases). Conditioning regimens were MAC in 18 cases (42%) and RIC/NMA in 25 cases (58%, table 2).

Four patients (9%) had engraftment failure or secondary graft rejection, 3 of whom having received cord blood units. All these 4 patients were transplanted again 2 to 17 weeks after the first transplant.

After a mean follow-up of 668 days for the entire cohort (1050 days for alive patients), 22 patients (51.2%) were alive, 19 of whom being disease-free (44.2%). Eleven patients had relapsed, at a median of 225 days post-HSCT (range: 74-821 days). Two-year cumulative incidences of relapse (CIR) and non-relapse mortality (NRM) were 25.5% (95% CI = [0.13-0.40]) and 32.8% (95% CI = [0.186-0.479]) respectively (figure 1). At 2 years post-transplant, disease-free survival (DFS) and overall survival (OS) were 44.9% (95% CI = [0.291-0.595]) and 52.2% (95% CI = [0.357-0.664]), respectively. Even though not statistically significant, patients receiving a MAC (n = 18) were less likely to relapse than patients receiving RIC/NMA (2-year CIR = 7.1% and 36% respectively, P = 0.137), but had a higher NRM rate (43.9% versus 26% at 2 years, P = 0.419), resulting in similar 2-year DFS and OS (57.1% versus 38%, P = 0.511 and 57.1% versus 49.7%, P = 0.91). There was a trend for a lower incidence of NRM at 2 years in patients transplanted from a sibling donor versus others (16.7% and 39.9% respectively, P = 0.0505, figure 2), but donor source had no effect on CIR (P = 0.826), DFS (P = 0.194) and OS (P = 0.188).

Conclusion

In this series of 43 patients with BPDCN, allogeneic HSCT was associated with a good disease control, but NRM was high. In this regard, transplantation from a sibling donor appears to be the best option. RIC/NMA are feasible and may also reduce the incidence of NRM, but at the expense of a higher incidence of relapse.

Table 1.

Patients' characteristics

N43
Age 57 (20-72) 
Sex (M/F) 29/14 
Time from diagnosis (days) 170 (107-1050) 
Disease status at HSCT  
 CR1  34 (79%) 
 CR2  5 (12%) 
 No CR  2 (5%) 
 Unknown  2 (5%) 
Donor  
 Sibling  18 (42%) 
 Unrelated  23 (53%) 
 Mismatch relative  2 (5%) 
Cell source  
 Bone Marrow  7 (16%) 
 Peripheral Blood  30 (70%) 
 Cord Blood  6 (14%) 
Conditioning regimen  
 MAC  18 (42%) 
 RIC/NMA  25 (58%) 
CMV status (D/R)  
 -/-  18 (42%) 
 -/+  9 (21%) 
 +/-  4 (9%) 
 +/+  12 (28%) 
GVHD prophylaxis  
 Ciclo/MTX  15 (35%) 
 Ciclo/MMF  19 (44%) 
 Ciclo alone  5 (12%) 
 Other  2 (5%) 
 Unknown  2 (5%) 
N43
Age 57 (20-72) 
Sex (M/F) 29/14 
Time from diagnosis (days) 170 (107-1050) 
Disease status at HSCT  
 CR1  34 (79%) 
 CR2  5 (12%) 
 No CR  2 (5%) 
 Unknown  2 (5%) 
Donor  
 Sibling  18 (42%) 
 Unrelated  23 (53%) 
 Mismatch relative  2 (5%) 
Cell source  
 Bone Marrow  7 (16%) 
 Peripheral Blood  30 (70%) 
 Cord Blood  6 (14%) 
Conditioning regimen  
 MAC  18 (42%) 
 RIC/NMA  25 (58%) 
CMV status (D/R)  
 -/-  18 (42%) 
 -/+  9 (21%) 
 +/-  4 (9%) 
 +/+  12 (28%) 
GVHD prophylaxis  
 Ciclo/MTX  15 (35%) 
 Ciclo/MMF  19 (44%) 
 Ciclo alone  5 (12%) 
 Other  2 (5%) 
 Unknown  2 (5%) 

Table 2.

Conditioning regimens

MAC 14 
Cy/TBI 11 
 Cy/TBI 12 Gy  
 Cy/TBI 10 Gy  
 Cy/Flu/TBI 12 Gy  
Bu/Cy 
RIC/NMA 29 
Flu/Bu/ALG 10 
Flu/TBI 2 Gy 10 
 Flu/TBI 2 Gy  
 Cy/Flu/TBI 2 Gy  
 AraC/Flu/TBI 2 Gy  
Sequential 
 Amsa/AraC/Flu/Cy/Bu/ALG  
 Amsa/AraC/Flu/Cy/TBI 2 Gy/ALG  
 Amsa/AraC/Flu/Bu/ALG  
Flu/Bu/Thiotepa/ALG 
Flu/Mel 
Cy/TBI 8 Gy 
TLI/ALG 
MAC 14 
Cy/TBI 11 
 Cy/TBI 12 Gy  
 Cy/TBI 10 Gy  
 Cy/Flu/TBI 12 Gy  
Bu/Cy 
RIC/NMA 29 
Flu/Bu/ALG 10 
Flu/TBI 2 Gy 10 
 Flu/TBI 2 Gy  
 Cy/Flu/TBI 2 Gy  
 AraC/Flu/TBI 2 Gy  
Sequential 
 Amsa/AraC/Flu/Cy/Bu/ALG  
 Amsa/AraC/Flu/Cy/TBI 2 Gy/ALG  
 Amsa/AraC/Flu/Bu/ALG  
Flu/Bu/Thiotepa/ALG 
Flu/Mel 
Cy/TBI 8 Gy 
TLI/ALG 

Figure 1.

Cumulative incidences of relapse and non-relapse mortality

Figure 1.

Cumulative incidences of relapse and non-relapse mortality

Figure 2.

Non-relapse mortality according to donor type

Figure 2.

Non-relapse mortality according to donor type

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.