Background

Philadelphia negative myeloproliferative or myeloproliferative/myelodysplastic neoplasms may evolve towards secondary acute myeloid leukemia (AML). The prognosis of such secondary leukemia is very poor. At present, there are only a few reports assessing the outcome of adult patients with a philadelphia negative myeloproliferative or myeloproliferative/myelodysplastic neoplasm in blast phase (MPN-BP) who received allogeneic stem cell transplantation (allo-SCT).

Patients and Methods

in this retrospective study, inclusion criteria were: (i) adult patients with a MPN-BP (ii) who received first allo-SCT (iii) between 2000 and 2010 (iv) irrespective of the stem cell source or conditioning regimen. MPN with <20% blasts in blood/bone marrow and AML secondary to myelodysplastic syndromes were excluded from this analysis.

Results

60 patients were included. MPN, AML and allo-SCT characteristics are described in table 1. Median age at allo-SCT was 57 (range, 30-68). Patients received allo-SCT in first complete remission (CR1), CR2 or in advanced disease in 22 (37%), 4 (7%) and 34(57%) of cases, respectively. Engraftment was achieved in 55 cases (92%). With a median follow-up of 31 months (range, 25-44), the 3-year overall survival (OS) and Leukemia-Free-Survival (LFS) were respectively 18% and 9%. The 3-year transplant-related mortality (TRM) was 24% whereas relapse incidence was 68%. The 3-year LFS of patients grafted in CR (n=26) was 18% whereas the 3-year LFS of patients allografted in advanced disease (n=34) was only 3% (p=0.008). In the CR group, the 3-year TRM was 24% whereas relapse incidence was 61%. Intermediate or good AML karyotype (3-year LFS of 33% versus 10% for adverse AML karyotype, p=0.03) and the absence of a previous thrombotic event (3-year LFS of 24% versus 0, p=0.02) were associated with an improved LFS in patients allografted in CR.

Table 1

MPN and AML characteristics

N60
Patient gender Male: 46 (77%) 
MPN Myeloproliferative neoplasms: 43
Polycythemia vera: 10
Essential Thrombocytemia: 20
Primary myelofibrosis: 8
Other: 5
Myelodysplastic/myeloproliferative neoplasms: 17
Chronic myelomonocytic leukemia: 15
Other: 2 
Time from MPN diagnosis to blast phase (months) 66 (range, 4-330) 
Median age at time allo-SCT (years) 57 (range, 30-68) 
AML karyotype Favorable: 1
Normal: 16
Other intermediate risk: 9
Adverse: 25
Failed: 9 
AML therapy before allo-SCT Intensive chemotherapy: 50
Hypomethylating agent: 6
Upfront allo-SCT: 7 
AML status at allo-SCT CR1: 22
CR>1: 4
advanced: 34 
Stem cell source Bone Marrow: 10
Peripheral Blood Stem Cell: 44
Cord Blood: 6 
Conditioning regimen Myeloablative: 14
Reduced-intensity regimen: 33
Sequential regimen: 13 
N60
Patient gender Male: 46 (77%) 
MPN Myeloproliferative neoplasms: 43
Polycythemia vera: 10
Essential Thrombocytemia: 20
Primary myelofibrosis: 8
Other: 5
Myelodysplastic/myeloproliferative neoplasms: 17
Chronic myelomonocytic leukemia: 15
Other: 2 
Time from MPN diagnosis to blast phase (months) 66 (range, 4-330) 
Median age at time allo-SCT (years) 57 (range, 30-68) 
AML karyotype Favorable: 1
Normal: 16
Other intermediate risk: 9
Adverse: 25
Failed: 9 
AML therapy before allo-SCT Intensive chemotherapy: 50
Hypomethylating agent: 6
Upfront allo-SCT: 7 
AML status at allo-SCT CR1: 22
CR>1: 4
advanced: 34 
Stem cell source Bone Marrow: 10
Peripheral Blood Stem Cell: 44
Cord Blood: 6 
Conditioning regimen Myeloablative: 14
Reduced-intensity regimen: 33
Sequential regimen: 13 
Conclusion

These results suggest that the outcome of patients with a MPN-BP is dismal despite allo-SCT due to a high relapse incidence even in patients transplanted in CR. Outside a clinical trial, allo-SCT should be mainly proposed to patients in CR. New strategies are mandatory to improve the outcome of patients in blast phase.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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