Contributions
Abstract: EP1100
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
The myeloproliferative neoplasms (MPN) comprise a group of hematological malignancies, consisting of essential thrombocytosis (ET), polycythemia vera (PV), and primary myelofibrosis (MF) which are diagnosed primarily in older adults (OA). MPN is characterized by clonal overproduction of mature blood cells and a driver mutation in the JAK2, MPL, or CALR gene. However, MPN in pediatric and young adults (PAYA) has not been well-described and optimal management is unknown.
Aims
We sought to compare genomic features, disease progression, and clinical outcomes between the PAYA and OA patient groups.
Methods
The Hopkins MPN cohort is comprised of 630 patients with an MPN enrolled between 2005-2015. All had driver mutation genotyping for JAK2V617F, CALR, and MPL. PAYA was defined as those diagnosed ≤39 years of age; OA were diagnosed at >40 years. STADA was used for statistical analysis. Familial MPN was defined as MPN with a 1st or 2nd degree relative with myeloid malignancy.
Results
Of 630 patients, 27% (n=171) were PAYA (average age 30 years; range 1 week-39 years) and 63% (n=459) were OA (average age 58 years; range 40-89 years). Females comprised the majority in both cohorts, but were more prevalent in PAYA (71% v. 58%; p<0.05). ET was more frequent in PAYA compared to OA (67% v. 39%; p<0.05), whereas PV [26% v. 46%; p<0.05) and MF [7% v. 16%; p<0.05) were less common. Mutations in JAK2 V617F (64% PAYA, 80% OA) or exon 12 mutations (2% PAYA, 1% OA) comprised 100% of PV for both groups, while JAK2 mutations were less common in PAYA ET (55% v. 67%; p<0.05) and similar in MF (42% v. 66%). CALR mutations were similar in PAYA and OA in ET, but less common in PAYA MF (42% v. 16%; p<0.05). MPL mutations were more common in PAYA MF (42% v. 17%). Triple negative disease (absence of mutations in JAK, CALR, MPL) was more common in PAYA (9% v. 4%; p<0.05). Familial MPN was more prevalent (19% v. 9%; p<0.05). Cancer predisposition syndromes were rare in both cohorts (2 PAYA, 1 OA). Venous thromboses comprised the most frequent (n=39; 23%) complication in PAYA. Additional cancers, most frequently skin, developed in 9% of PAYA compared to 20% (p<0.05) of OA. In PAYA, 12.9% progressed to MF or AML, with majority progressing to MF (11%). In PAYA, ET progressed to MF (n=8, mean age 51 years, mean time to progression 22 years) and PV to MF (n=11, mean age 40 years, mean time to progression 10 years). Progression to AML occurred in 2% (3/171) PAYA, with average time to AML from original MPN diagnosis of 27 years, compared to OA, where AML occurred in 5% (25/459), with average time to AML progression of 11 years (p<0.05). There were fewer deaths in the PAYA v. OA (12% v. 39%; p<0.05). Overall survival was longer in PAYA (29 v. 12 years, p<0.05); however, average age of death was lower in the PAYA v. OA (60 v. 74 years; p<0.05).
Conclusion
PAYA comprised almost 1/3 of our MPN cohort and were more likely to present with lower-risk disease (ET), although almost 13% ultimately progressed to MF or AML. PAYA MPN had longer latency periods before progression and longer overall survival but earlier age of death compared OA MPN. The higher prevalence of familial MPN in PAYA and the secondary cancers suggest that an inherited predisposition to cancer may contribute to MPN development. Together, our findings suggest that PAYA patients should be followed closely for progression, venous thromboses, and possibly additional cancers. The long latency underscores the need to limit exposure to potentially genotoxic therapies.
Keyword(s): Essential Thrombocytemia, Myelofibrosis, Myeloproliferative disorder, Polycythemia vera
Abstract: EP1100
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
The myeloproliferative neoplasms (MPN) comprise a group of hematological malignancies, consisting of essential thrombocytosis (ET), polycythemia vera (PV), and primary myelofibrosis (MF) which are diagnosed primarily in older adults (OA). MPN is characterized by clonal overproduction of mature blood cells and a driver mutation in the JAK2, MPL, or CALR gene. However, MPN in pediatric and young adults (PAYA) has not been well-described and optimal management is unknown.
Aims
We sought to compare genomic features, disease progression, and clinical outcomes between the PAYA and OA patient groups.
Methods
The Hopkins MPN cohort is comprised of 630 patients with an MPN enrolled between 2005-2015. All had driver mutation genotyping for JAK2V617F, CALR, and MPL. PAYA was defined as those diagnosed ≤39 years of age; OA were diagnosed at >40 years. STADA was used for statistical analysis. Familial MPN was defined as MPN with a 1st or 2nd degree relative with myeloid malignancy.
Results
Of 630 patients, 27% (n=171) were PAYA (average age 30 years; range 1 week-39 years) and 63% (n=459) were OA (average age 58 years; range 40-89 years). Females comprised the majority in both cohorts, but were more prevalent in PAYA (71% v. 58%; p<0.05). ET was more frequent in PAYA compared to OA (67% v. 39%; p<0.05), whereas PV [26% v. 46%; p<0.05) and MF [7% v. 16%; p<0.05) were less common. Mutations in JAK2 V617F (64% PAYA, 80% OA) or exon 12 mutations (2% PAYA, 1% OA) comprised 100% of PV for both groups, while JAK2 mutations were less common in PAYA ET (55% v. 67%; p<0.05) and similar in MF (42% v. 66%). CALR mutations were similar in PAYA and OA in ET, but less common in PAYA MF (42% v. 16%; p<0.05). MPL mutations were more common in PAYA MF (42% v. 17%). Triple negative disease (absence of mutations in JAK, CALR, MPL) was more common in PAYA (9% v. 4%; p<0.05). Familial MPN was more prevalent (19% v. 9%; p<0.05). Cancer predisposition syndromes were rare in both cohorts (2 PAYA, 1 OA). Venous thromboses comprised the most frequent (n=39; 23%) complication in PAYA. Additional cancers, most frequently skin, developed in 9% of PAYA compared to 20% (p<0.05) of OA. In PAYA, 12.9% progressed to MF or AML, with majority progressing to MF (11%). In PAYA, ET progressed to MF (n=8, mean age 51 years, mean time to progression 22 years) and PV to MF (n=11, mean age 40 years, mean time to progression 10 years). Progression to AML occurred in 2% (3/171) PAYA, with average time to AML from original MPN diagnosis of 27 years, compared to OA, where AML occurred in 5% (25/459), with average time to AML progression of 11 years (p<0.05). There were fewer deaths in the PAYA v. OA (12% v. 39%; p<0.05). Overall survival was longer in PAYA (29 v. 12 years, p<0.05); however, average age of death was lower in the PAYA v. OA (60 v. 74 years; p<0.05).
Conclusion
PAYA comprised almost 1/3 of our MPN cohort and were more likely to present with lower-risk disease (ET), although almost 13% ultimately progressed to MF or AML. PAYA MPN had longer latency periods before progression and longer overall survival but earlier age of death compared OA MPN. The higher prevalence of familial MPN in PAYA and the secondary cancers suggest that an inherited predisposition to cancer may contribute to MPN development. Together, our findings suggest that PAYA patients should be followed closely for progression, venous thromboses, and possibly additional cancers. The long latency underscores the need to limit exposure to potentially genotoxic therapies.
Keyword(s): Essential Thrombocytemia, Myelofibrosis, Myeloproliferative disorder, Polycythemia vera