SPLENOMEGALY AND ELEVATED ALKALINE PHOSPHATASE ARE STRONG AND INDEPENDENTADVERSE PROGNOSTIC MARKERS IN PATIENTS WITH SYSTEMIC MASTOCYTOSIS
(Abstract release date: 05/19/16)
EHA Library. Jawhar M. 06/09/16; 132898; E1349
Dr. Mohamad Jawhar
Contributions
Contributions
Abstract
Abstract: E1349
Type: Eposter Presentation
Background
Systemic mastocytosis (SM) comprises a group of rare myeloid neoplasms characterized by accumulation of mast cells (MC) in various tissues, predominantly skin, bone marrow (BM), and visceral organs. Depending on the affected organ(s), SM-related organ damage, and involvement of other hematopoietic lineages, SM can be divided into indolent SM (ISM) and advanced SM (advSM). The KIT D816V mutation is a primary driver of disease manifestations while the presence and number of additional mutations, e.g. in SRSF2, ASXL, or RUNX1 (S/A/R gene panel), have a strong adverse impact on disease phenotype and prognosis. However, only little is yet known about the prognostic impact of aberrant clinical, laboratory or hematological parameters.
Aims
We sought to evaluate the influence of organomegaly, as measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen as well as other known clinical and hematological characteristics, on disease evolution and overall survival (OS) in SM.
Methods
We retrospectively analyzed 108 patients (median age 64 years, range 27-82; male 57%) with ISM (n=41) or advSM (n=67) (aggressive SM/mast cell leukemia [ASM/MCL], n=12 or SM/ASM/MCL with associated hematologic non-mast cell lineage disease [AHNMD], n=55). Median observation time from the date of MRI was 26 months (range 1-79); 33/108 (31%) patients have died in the observation period. The 2-year OS probability of all patients was 77%, with a median OS of 5.4 years.
Results
The median volumes of liver and spleen were 2035 mL (range 1034-4265) and 540 mL (range 92-3193), respectively. Overall, MRI-documented hepatomegaly (>2400 mL) was observed in 31/108 (29%) patients, and splenomegaly in 67/108 (62%) patients (ISM 12%, advSM 88%). Splenomegaly was mild (≥ 450 mL) in 43/67 (64%) patients and marked (≥ 1200 mL) in 24/67 (36%) patients. High disease burden, presence of an AHNMD and organ damage (C-findings) were strongly associated with mildly or markedly increased spleen volume (P<0.05). In multivariate analysis, however, only an increased spleen volume ≥450 mL (hazard ratio [HR], 9.4; 95% confidence interval [CI], [2.2-39.9]; P=0.0002) and an elevated alkaline phosphatase (AP; HR 8.4 [3.2-22.1]; P<0.0001) remained independent predictive adverse prognostic markers for OS. The 2-year OS was 100%, 76%, and 56%, respectively (P<0.001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. If available (n=74), the relative frequency of mutations in the S/A/R gene panel was significantly different in the various risk groups (low: 0/15, intermediate: 12/24 [50%], high: 28/35 [80%], P<0.01).
Conclusion
Splenomegaly and elevated AP provide relevant prognostic information in SM patients that is independent of other clinical, laboratory or hematological parameters. In addition to the recently identified adverse prognostic impact of mutations in the S/A/R gene panel, this data will have major implications for the implementation and validation of novel prognostic scoring systems on the basis of larger patient cohorts, such as the dataset of the ECNM registry, with the long-term objective to develop an IPSS for patients with SM.
Session topic: E-poster
Keyword(s): Prognostic factor, Systemic mastocytosis
Type: Eposter Presentation
Background
Systemic mastocytosis (SM) comprises a group of rare myeloid neoplasms characterized by accumulation of mast cells (MC) in various tissues, predominantly skin, bone marrow (BM), and visceral organs. Depending on the affected organ(s), SM-related organ damage, and involvement of other hematopoietic lineages, SM can be divided into indolent SM (ISM) and advanced SM (advSM). The KIT D816V mutation is a primary driver of disease manifestations while the presence and number of additional mutations, e.g. in SRSF2, ASXL, or RUNX1 (S/A/R gene panel), have a strong adverse impact on disease phenotype and prognosis. However, only little is yet known about the prognostic impact of aberrant clinical, laboratory or hematological parameters.
Aims
We sought to evaluate the influence of organomegaly, as measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen as well as other known clinical and hematological characteristics, on disease evolution and overall survival (OS) in SM.
Methods
We retrospectively analyzed 108 patients (median age 64 years, range 27-82; male 57%) with ISM (n=41) or advSM (n=67) (aggressive SM/mast cell leukemia [ASM/MCL], n=12 or SM/ASM/MCL with associated hematologic non-mast cell lineage disease [AHNMD], n=55). Median observation time from the date of MRI was 26 months (range 1-79); 33/108 (31%) patients have died in the observation period. The 2-year OS probability of all patients was 77%, with a median OS of 5.4 years.
Results
The median volumes of liver and spleen were 2035 mL (range 1034-4265) and 540 mL (range 92-3193), respectively. Overall, MRI-documented hepatomegaly (>2400 mL) was observed in 31/108 (29%) patients, and splenomegaly in 67/108 (62%) patients (ISM 12%, advSM 88%). Splenomegaly was mild (≥ 450 mL) in 43/67 (64%) patients and marked (≥ 1200 mL) in 24/67 (36%) patients. High disease burden, presence of an AHNMD and organ damage (C-findings) were strongly associated with mildly or markedly increased spleen volume (P<0.05). In multivariate analysis, however, only an increased spleen volume ≥450 mL (hazard ratio [HR], 9.4; 95% confidence interval [CI], [2.2-39.9]; P=0.0002) and an elevated alkaline phosphatase (AP; HR 8.4 [3.2-22.1]; P<0.0001) remained independent predictive adverse prognostic markers for OS. The 2-year OS was 100%, 76%, and 56%, respectively (P<0.001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. If available (n=74), the relative frequency of mutations in the S/A/R gene panel was significantly different in the various risk groups (low: 0/15, intermediate: 12/24 [50%], high: 28/35 [80%], P<0.01).
Conclusion
Splenomegaly and elevated AP provide relevant prognostic information in SM patients that is independent of other clinical, laboratory or hematological parameters. In addition to the recently identified adverse prognostic impact of mutations in the S/A/R gene panel, this data will have major implications for the implementation and validation of novel prognostic scoring systems on the basis of larger patient cohorts, such as the dataset of the ECNM registry, with the long-term objective to develop an IPSS for patients with SM.
Session topic: E-poster
Keyword(s): Prognostic factor, Systemic mastocytosis
Abstract: E1349
Type: Eposter Presentation
Background
Systemic mastocytosis (SM) comprises a group of rare myeloid neoplasms characterized by accumulation of mast cells (MC) in various tissues, predominantly skin, bone marrow (BM), and visceral organs. Depending on the affected organ(s), SM-related organ damage, and involvement of other hematopoietic lineages, SM can be divided into indolent SM (ISM) and advanced SM (advSM). The KIT D816V mutation is a primary driver of disease manifestations while the presence and number of additional mutations, e.g. in SRSF2, ASXL, or RUNX1 (S/A/R gene panel), have a strong adverse impact on disease phenotype and prognosis. However, only little is yet known about the prognostic impact of aberrant clinical, laboratory or hematological parameters.
Aims
We sought to evaluate the influence of organomegaly, as measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen as well as other known clinical and hematological characteristics, on disease evolution and overall survival (OS) in SM.
Methods
We retrospectively analyzed 108 patients (median age 64 years, range 27-82; male 57%) with ISM (n=41) or advSM (n=67) (aggressive SM/mast cell leukemia [ASM/MCL], n=12 or SM/ASM/MCL with associated hematologic non-mast cell lineage disease [AHNMD], n=55). Median observation time from the date of MRI was 26 months (range 1-79); 33/108 (31%) patients have died in the observation period. The 2-year OS probability of all patients was 77%, with a median OS of 5.4 years.
Results
The median volumes of liver and spleen were 2035 mL (range 1034-4265) and 540 mL (range 92-3193), respectively. Overall, MRI-documented hepatomegaly (>2400 mL) was observed in 31/108 (29%) patients, and splenomegaly in 67/108 (62%) patients (ISM 12%, advSM 88%). Splenomegaly was mild (≥ 450 mL) in 43/67 (64%) patients and marked (≥ 1200 mL) in 24/67 (36%) patients. High disease burden, presence of an AHNMD and organ damage (C-findings) were strongly associated with mildly or markedly increased spleen volume (P<0.05). In multivariate analysis, however, only an increased spleen volume ≥450 mL (hazard ratio [HR], 9.4; 95% confidence interval [CI], [2.2-39.9]; P=0.0002) and an elevated alkaline phosphatase (AP; HR 8.4 [3.2-22.1]; P<0.0001) remained independent predictive adverse prognostic markers for OS. The 2-year OS was 100%, 76%, and 56%, respectively (P<0.001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. If available (n=74), the relative frequency of mutations in the S/A/R gene panel was significantly different in the various risk groups (low: 0/15, intermediate: 12/24 [50%], high: 28/35 [80%], P<0.01).
Conclusion
Splenomegaly and elevated AP provide relevant prognostic information in SM patients that is independent of other clinical, laboratory or hematological parameters. In addition to the recently identified adverse prognostic impact of mutations in the S/A/R gene panel, this data will have major implications for the implementation and validation of novel prognostic scoring systems on the basis of larger patient cohorts, such as the dataset of the ECNM registry, with the long-term objective to develop an IPSS for patients with SM.
Session topic: E-poster
Keyword(s): Prognostic factor, Systemic mastocytosis
Type: Eposter Presentation
Background
Systemic mastocytosis (SM) comprises a group of rare myeloid neoplasms characterized by accumulation of mast cells (MC) in various tissues, predominantly skin, bone marrow (BM), and visceral organs. Depending on the affected organ(s), SM-related organ damage, and involvement of other hematopoietic lineages, SM can be divided into indolent SM (ISM) and advanced SM (advSM). The KIT D816V mutation is a primary driver of disease manifestations while the presence and number of additional mutations, e.g. in SRSF2, ASXL, or RUNX1 (S/A/R gene panel), have a strong adverse impact on disease phenotype and prognosis. However, only little is yet known about the prognostic impact of aberrant clinical, laboratory or hematological parameters.
Aims
We sought to evaluate the influence of organomegaly, as measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen as well as other known clinical and hematological characteristics, on disease evolution and overall survival (OS) in SM.
Methods
We retrospectively analyzed 108 patients (median age 64 years, range 27-82; male 57%) with ISM (n=41) or advSM (n=67) (aggressive SM/mast cell leukemia [ASM/MCL], n=12 or SM/ASM/MCL with associated hematologic non-mast cell lineage disease [AHNMD], n=55). Median observation time from the date of MRI was 26 months (range 1-79); 33/108 (31%) patients have died in the observation period. The 2-year OS probability of all patients was 77%, with a median OS of 5.4 years.
Results
The median volumes of liver and spleen were 2035 mL (range 1034-4265) and 540 mL (range 92-3193), respectively. Overall, MRI-documented hepatomegaly (>2400 mL) was observed in 31/108 (29%) patients, and splenomegaly in 67/108 (62%) patients (ISM 12%, advSM 88%). Splenomegaly was mild (≥ 450 mL) in 43/67 (64%) patients and marked (≥ 1200 mL) in 24/67 (36%) patients. High disease burden, presence of an AHNMD and organ damage (C-findings) were strongly associated with mildly or markedly increased spleen volume (P<0.05). In multivariate analysis, however, only an increased spleen volume ≥450 mL (hazard ratio [HR], 9.4; 95% confidence interval [CI], [2.2-39.9]; P=0.0002) and an elevated alkaline phosphatase (AP; HR 8.4 [3.2-22.1]; P<0.0001) remained independent predictive adverse prognostic markers for OS. The 2-year OS was 100%, 76%, and 56%, respectively (P<0.001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. If available (n=74), the relative frequency of mutations in the S/A/R gene panel was significantly different in the various risk groups (low: 0/15, intermediate: 12/24 [50%], high: 28/35 [80%], P<0.01).
Conclusion
Splenomegaly and elevated AP provide relevant prognostic information in SM patients that is independent of other clinical, laboratory or hematological parameters. In addition to the recently identified adverse prognostic impact of mutations in the S/A/R gene panel, this data will have major implications for the implementation and validation of novel prognostic scoring systems on the basis of larger patient cohorts, such as the dataset of the ECNM registry, with the long-term objective to develop an IPSS for patients with SM.
Session topic: E-poster
Keyword(s): Prognostic factor, Systemic mastocytosis
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