Factors Affecting the Results of Allogeneic Hematopoietic Stem Cell Transplantation in Hematologic Malignancies

Mehta, J.; Frankfurt, O.; Altman, J.; Evens, Andrew M; Gordon, L.; Tallman, M.; Williams, S.; Winter, J.; Krishnamurthy, J.; Grinblatt, D.; Kaminer, L.; Singhal, S.

doi:10.1182/blood.V112.11.4386.4386

Abstract

130 patients who were unsuitable for conventional-intensity conditioning underwent RI-HSCT after 100 mg/m² melphalan (+ 50 mg/kg cyclophosphamide if no prior autograft). GVHD prophylaxis comprised cyclosporine (HLA-matched siblings) or tacrolimus (all others) and MMF.

Table 1: Patient characteristics

Age (y)	19–71 (median 55)
Male	55%
Refractory disease	57%
ECOG performance status	0 34%
	1 48%
	2 14%
	3 4%
Diagnosis	Lymphoma 42%
	Leukemia 36%
	Myeloma 22%
Donor	Matched sibling 49%
	Mismatched sibling 2%
	Matched unrelated 33%
	Mismatched unrelated 15%
Donor age (y)	21–71 (median 44; 45% >45)
Male donor	65%
Prior autograft	45%

Age (y)	19–71 (median 55)
Male	55%
Refractory disease	57%
ECOG performance status	0 34%
	1 48%
	2 14%
	3 4%
Diagnosis	Lymphoma 42%
	Leukemia 36%
	Myeloma 22%
Donor	Matched sibling 49%
	Mismatched sibling 2%
	Matched unrelated 33%
	Mismatched unrelated 15%
Donor age (y)	21–71 (median 44; 45% >45)
Male donor	65%
Prior autograft	45%

Refractory disease, HLA mismatch, donor age >45, elevated creatinine, low DLCO, thrombocytopenia, male donor, poor performance status, and low albumin affected OS adversely in univariate analysis. The following factors affected outcome independently:

Table 2: Cox analysis

Adverse variable	Relative risk	P
TRM
HLA mismatch	4.78	0.0003
Performance status 2–3	3.07	0.044
Relapse
Donor age >45 y	2.0	0.012
Male donor	1.98	0.026
Refractory disease	1.84	0.05
EFS
Performance status 2–3	0.48	0.022
HLA mismatch	0.53	0.023
Refractory disease	0.55	0.016
Male donor	0.61	0.039
Donor age >45 y	0.63	0.034
OS
Performance status 2–3	0.44	0.025
HLA mismatch	0.31	0.0001
Refractory disease	0.49	0.007
Donor age >45 y	0.55	0.012
High LDH	0.53	0.007
Platelets <100	0.58	0.021

Adverse variable	Relative risk	P
TRM
HLA mismatch	4.78	0.0003
Performance status 2–3	3.07	0.044
Relapse
Donor age >45 y	2.0	0.012
Male donor	1.98	0.026
Refractory disease	1.84	0.05
EFS
Performance status 2–3	0.48	0.022
HLA mismatch	0.53	0.023
Refractory disease	0.55	0.016
Male donor	0.61	0.039
Donor age >45 y	0.63	0.034
OS
Performance status 2–3	0.44	0.025
HLA mismatch	0.31	0.0001
Refractory disease	0.49	0.007
Donor age >45 y	0.55	0.012
High LDH	0.53	0.007
Platelets <100	0.58	0.021

These prognostic factors were similar to those found on studying the first 63 patients in this series (Mehta et al. Bone Marrow Transplant 2006) –with the additional emergence of HLA mismatch and thrombocytopenia which were significant in univariate but not multivariate analysis then.

These data suggest that RI-HSCT is useful for some patients with hematologic malignancies who are ineligible for conventional-intensity HSCT. However, alternative HSCT techniques or non-HSCT options are needed for high-risk patients.

Figure 1