Enlarged Spleen Prior to Allogeneic Transplantation for Myelofibrosis Is Associated with Poor Engraftment and Increased Non-Relapse Mortality

Enlarged spleen prior to allogeneic transplantation for myelofibrosis is associated with poor engraftment and increased non-relapse mortality

Introduction

Allogeneic stem cell transplantation (SCT) is potentially curative for patients with Myelofibrosis (MF). However, treatment failure is common and often associated with slow engraftment or graft failure, risk factors for which are poorly defined.  

Patients

From 2000 to 2014, 30 adult patients (median age, 49 (range 18-68) underwent SCT for primary or secondary MF at WCMC/NYP. All patients received PBSC from matched related (MRD-14) or matched unrelated donors (MUD-16).  Most patients received fludarabine and melphalan (n=22) conditioning. ATG or alemtuzumab were used for patients who underwent MUD SCT. Only a minority of patients had low risk disease by DIPPS (26.7%) or Lille (20%) risk scores.  Twenty patients had splenomegaly, 6 by physical exam and 14 by imaging studies (median 24.5 Cm, range 16.2-34)

Results

After a median follows up of 49.5 months (range 3 to 154 months), the 4-year OS and RFS are 44% (95%CI: 29% - 67%) and 37% (95%CI: 23%-61%) respectively.  Neutrophil engraftment by day 18 occurred in 63% of patients. Platelets were engrafted by day 25 in 41% of patients. We used a Fine and Gray's proportional subdistribution hazard model. Splenomegaly was associated with delayed neutrophil engraftment (SHR=0.42, 95%CI= 0.21, 0.83, p=0.01), delayed platelet engraftment (SHR=0.18, 95%CI= 0.07, 0.48, p<0.001) and non-relapse mortality (NRM) (SHR=3.24, 95%CI= 0.94, 11.2, p=0.06). Elevated LDH was associated with delayed platelet engraftment (SHR=0.39, 95%CI= (0.16, 0.94), p=0.04) and NRM (SHR=2.82, 95%CI= 1.08, 7.35, p=0.03). MUD grafts were marginally associated with delayed neutrophil engraftment (SHR=0.55, 95%CI= 0.27, 1.12, p<0.10) but not platelet engraftment or NRM.

Conclusion

Splenomegaly contributed to delayed neutrophil and platelet engraftment and NRM. Splenectomy should be considered for patients with splenomegaly in need of transplantation.  Elevated LDH was associated with delayed platelets engraftment and NRM and might indicate more aggressive disease.

Patients	Characteristics
Age Median (Range)	49	(18-68)
Sex
Male	20	(67%)
Female	10	(33%)
Disease Risk at HSCT
Lille
Low	6	(20%)
Intermediate	15	(50%)
High	9	(30%)
DIPPS
Low	2	(6%)
Intermediate-1	6	(20%)
Intermediate-2	17	(57%)
High	5	(17%)
JAK 2 Kinase
Positive	11	(37%)
Negative	11	(37%)
Unknown	8	(24)
Spleen
Enlarged	18	(60%)
Normal	4	(13%)
Removed	8	(27%)
Albumin 1
Median	3.9
Min	2.6
Max	4.9
LDH 2
Median	487
Min	126
Max	1304
ECOG
0	5
1	17
2 Unknown	4 4

¹ Albumin normal value: 3.5-4.8 g/dl

² LDH normal value: 98-192 IU/L