Diabetes and Second Neoplasia Impact on Prognosis in Pre-Fibrotic Primary Myelofibrosis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Methods
2.2.1. Pre-PMF Molecular Analyses
2.2.2. Bone Marrow Biopsy
2.2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical-Laboratory Features | Patients (n = 378) |
---|---|
Male/Female | 174/204 |
Age (years), median (range) | 64.9 (18.9–91.9) |
Hb (g/dL), median (range) | 13.7 (6.8–19.7) |
Hct (%), median (range) | 41.6 (20.3–60.3) |
WBC count (×109/L), median (range) | 9.1 (2.1–42.6) |
PLT count (×109/L), median (range) | 687 (51–2513) |
Peripheral blood blasts ≥ 1%, n. (%) | 19 (5.0) |
LDH (IU/L), median (range) | 441.5 (119–2960) |
Serum erythropoietin (IU/L), median (range) | 6.6 (0.04–1002) |
Circulating CD34+ cells (/µL), median (range) | 5.0 (0–330) |
Constitutional symptoms, n. (%) | 38 (10.1) |
Palpable splenomegaly, n. (%) | 140 (37.0) |
IPSS, n. (%) | |
Low risk | 155 (41.0) |
Intermediate-1 risk | 178 (47.1) |
Intermediate-2 risk | 32 (8.5) |
High risk | 13 (3.4) |
DIPSS, n. (%) | |
Low risk | 155 (41.0) |
Intermediate-1 risk | 196 (51.8) |
Intermediate-2 risk | 26 (6.9) |
High risk | 1 (0.3) |
Cytogenetic abnormalities, n. (%) | 44 (11.6) |
JAK2V617F, n. (%) | 256 (67.7) |
JAK2 allele burden (%), median (range) | 29.0 (1.4–99.1) |
CALR mutations, n. (%) | 79 (20.9) |
Type 1 mutation, n. (%) | 47 (12.4) |
Type 2 mutation, n. (%) | 22 (5.8) |
Other mutations, n. (%) | 10 (2.7) |
MPL mutations, n. (%) | 10 (2.7) |
Triple-negative, n. (%) | 33 (8.7) |
Reticulin fibrosis grade, n. (%) | |
MF-0 | 142 (37.6) |
MF-1 | 236 (62.4) |
Comorbidities, n. (%) | |
Diabetes | 50 (13.2) |
SC | 102 (27.0) |
Hematologic malignancies | 8 (2.1) |
Non-hematologic malignancies | 94 (24.9) |
Thrombotic events, n. (%) | |
At diagnosis | 23 (6.1) |
During follow-up | 76 (20.1) |
Hemorrhagic events, n. (%) | |
At diagnosis | / |
During follow-up | 40 (10.6) |
Disease progression, n. (%) | |
overt PMF | 30 (7.9) |
AML | 25 (6.6) |
Deceased, n. (%) | 107 (28.3) |
Disease progression (including AML) | 28 (7.4) |
Thrombo-hemorrhagic events | 13 (3.5) |
Infectious complications | 14 (3.7) |
Other unrelated causes (including SC) | 25 (6.6) |
Unknown | 27 (7.1) |
Lost to follow-up, n. (%) | 78 (20.6) |
Cytoreductive/targeted therapy, n. (%) | 304 (80.4) |
Hydroxyurea | 292 (77.3) |
Ruxolitinib | 47 (12.4) |
Antiplatelet therapy, n. (%) | 309 (81.8) |
Covariate | All Patients (N) | Response Variable | Class Comparison | OR (95%CI) | p Value * | p Value *,$ |
---|---|---|---|---|---|---|
IPSS at diagnosis | 300 | Death | 1 vs. 0 | 3.47 (1.97–6.12) | <0.000 * | 0.813 |
IPSS at diagnosis | 300 | Death | 2 vs. 0 | 10.56 (4.41–25.3) | <0.000 * | |
DIPSS at diagnosis | 300 | Death | 1 vs. 0 | 3.5 (2.00–6.12) | <0.000 * | 0.442 |
DIPSS at diagnosis | 300 | Death | 2 vs. 0 | 20.66 (6.36–67.06) | <0.000 * | |
IPSS at diagnosis | 378 | Thrombosis ^ | 1 vs. 0 | 0.71 (0.43–1.17) | 0.302 | 0.675 |
IPSS at diagnosis | 378 | Thrombosis ^ | 2 vs. 0 | 0.63 (0.28–1.42) | 0.464 | |
DIPSS at diagnosis | 378 | Thrombosis ^ | 1 vs. 0 | 0.71 (0.44–1.15) | 0.291 | 0.834 |
DIPSS at diagnosis | 378 | Thrombosis ^ | 2 vs. 0 | 0.57 (0.20–1.61) | 0.452 | |
IPSS at diagnosis | 378 | Hemorrhage | 1 vs. 0 | 1.31 (0.62–2.74) | 0.584 | 0.985 |
IPSS at diagnosis | 378 | Hemorrhage | 2 vs. 0 | 1.68 (0.60–4.71) | 0.419 | |
DIPSS at diagnosis | 378 | Hemorrhage | 1 vs. 0 | 1.31 (0.63–2.71) | 0.541 | 0.896 |
DIPSS at diagnosis | 378 | Hemorrhage | 2 vs. 0 | 1.90 (0.57–6.33) | 0.377 | |
IPSS at diagnosis | 378 | Transformation # | 1 vs. 0 | 0.33 (0.16–0.66) | 0.007 * | 0.008 * |
IPSS at diagnosis | 378 | Transformation # | 2 vs. 0 | 0.77 (0.31–1.89) | 0.514 | |
DIPSS at diagnosis | 378 | Transformation # | 1 vs. 0 | 0.35 (0.18–0.67) | 0.006 * | 0.006 * |
DIPSS at diagnosis | 378 | Transformation # | 2 vs. 0 | 0.95 (0.33–2.71) | 0.362 | |
IPSS at diagnosis | 378 | Composite outcome ° | 1 vs. 0 | 0.60 (0.39–0.94) | 0.070 | 0.212 |
IPSS at diagnosis | 378 | Composite outcome ° | 2 vs. 0 | 0.65 (0.33–1.30) | 0.603 | |
DIPSS at diagnosis | 378 | Composite outcome ° | 1 vs. 0 | 0.60 (0.39–0.93) | 0.068 | 0.211 |
DIPSS at diagnosis | 378 | Composite outcome ° | 2 vs. 0 | 0.70 (0.30–1.62) | 0.795 |
Covariate | All Patients (N) | Class Comparison ° | OR (95%CI) | p Value * | p Value *,$ |
---|---|---|---|---|---|
Gender | 300 | M vs. F | 1.39 (0.87–2.23) | 0.174 | - |
IPSS at diagnosis ° | 300 | 1 vs. 0 | 3.47 (1.97–6.12) | <0.000 * | 0.813 |
IPSS at diagnosis ° | 300 | 2 vs. 0 | 10.56 (4.41–25.30) | <0.000 * | |
DIPSS at diagnosis ° | 300 | 1 vs. 0 | 3.50 (2.00–6.12) | <0.000 * | 0.442 |
DIPSS at diagnosis ° | 300 | 2 vs. 0 | 20.66 (6.36–67.06) | <0.000 * | |
Bone marrow fibrosis grade & | 300 | 1 vs. 0 | 0.93 (0.57–1.54) | 0.788 | - |
Driver mutations profile $1 | 300 | 1–2 vs. 0 | 1 vs. 0: 1.96 (0.89–4.33) | 0.242 | 0.172 |
2 vs. 0: 1.61 (0.52–4.99) | 0.769 | ||||
Driver mutations profile $2 | 300 | 1–5 vs. 0 | - | 0.551 | - |
Cytogenetic at diagnosis | 252 | 1 vs. 0 | 1.47 (0.72–3.01) | 0.287 | - |
Cytogenetic risk at diagnosis & | 252 | 1 vs. 0 | 1.00 (0.33–3.09) | 0.333 | 0.414 |
Cytogenetic risk at diagnosis & | 252 | 2 vs. 0 | 3.01 (0.70–12.90) | 0.161 | |
Splenomegaly | 297 | 1 vs. 0 | 1.49 (0.91–2.44) | 0.113 | - |
Erythropoietin # | 106 | 1 vs. 0 | 1.63 (0.70–3.78) | 0.256 | - |
Transfusions | 292 | 1 vs. 0 | 9.04 (4.60–17.75) | <0.000 * | - |
Smoke ^ | 291 | 1 vs. 0 | 1.75 (0.93–3.27) | 0.219 | 0.144 |
Smoke ^ | 291 | 2 vs. 0 | 1.14 (0.56–2.34) | 0.696 | |
Hypertension | 298 | 1 vs. 0 | 1.85 (1.14–2.99) | 0.012 * | - |
Diabetes | 300 | 1 vs. 0 | 2.99 (1.53–5.87) | 0.001 * | - |
Dyslipidemia | 300 | 1 vs. 0 | 1.19 (0.71–1.98) | 0.505 | - |
Family thrombosis history | 178 | 1 vs. 0 | 1.09 (0.55–2.19) | 0.801 | - |
Personal thrombosis history | 294 | 1 vs. 0 | 1.32 (0.74–2.34) | 0.349 | - |
Thrombophilia screening | 167 | 1 vs. 0 | 2.04 (1.02–4.11) | 0.045 * | - |
Second neoplasia | 300 | 1 vs. 0 | 2.59 (1.54–4.34) | 0.000 * | - |
Covariate | Class Comparison | OR (95%CI) | p Value * | p Value *,$ |
---|---|---|---|---|
IPSS at diagnosis ° | 1 vs. 0 | 3.34 (1.85–6.04) | <0.000 * | 0.841 |
IPSS at diagnosis ° | 2 vs. 0 | 12.55 (5.04–31.24) | <0.000 * | |
Diabetes * | 1 vs. 0 | 2.95 (1.41–6.18) | 0.004 * | - |
Second neoplasia * | 1 vs. 0 | 2.88 (1.63–5.07) | 0.000 * | - |
Covariate | Class Comparison | OR (95%CI) | p Value * | p Value *,$ |
---|---|---|---|---|
DIPSS at diagnosis ° | 1 vs. 0 | 3.40 (1.89–6.10) | <0.000 * | 0.257 |
DIPSS at diagnosis ° | 2 vs. 0 | 25.65 (7.62–86.42) | <0.000 * | |
Diabetes * | 1 vs. 0 | 2.89 (1.37–6.09) | 0.005 * | - |
Second neoplasia * | 1 vs. 0 | 2.97 (1.69–5.24) | 0.000 * | - |
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Cattaneo, D.; Vener, C.; Elli, E.M.; Bucelli, C.; Galli, N.; Cavalca, F.; Auteri, G.; Vincelli, D.; Martino, B.; Gianelli, U.; et al. Diabetes and Second Neoplasia Impact on Prognosis in Pre-Fibrotic Primary Myelofibrosis. Cancers 2022, 14, 1799. https://doi.org/10.3390/cancers14071799
Cattaneo D, Vener C, Elli EM, Bucelli C, Galli N, Cavalca F, Auteri G, Vincelli D, Martino B, Gianelli U, et al. Diabetes and Second Neoplasia Impact on Prognosis in Pre-Fibrotic Primary Myelofibrosis. Cancers. 2022; 14(7):1799. https://doi.org/10.3390/cancers14071799
Chicago/Turabian StyleCattaneo, Daniele, Claudia Vener, Elena Maria Elli, Cristina Bucelli, Nicole Galli, Fabrizio Cavalca, Giuseppe Auteri, Donatella Vincelli, Bruno Martino, Umberto Gianelli, and et al. 2022. "Diabetes and Second Neoplasia Impact on Prognosis in Pre-Fibrotic Primary Myelofibrosis" Cancers 14, no. 7: 1799. https://doi.org/10.3390/cancers14071799