Abstract
Survival of Essential Thrombocytemia (ET) patients in the first 10 years of disease follow-up is similar to the general population one. While it is well known that alkylating agents (given alone or sequentially) increase the risk for acute myeloid leukemia, the specific role of different therapies on the development of secondary malignancies (SM) in ET patients, is still under investigation.
To retrospectively evaluate the role of different treatments on the development of SM in a large population of ET patients.
We collected a series of 1026 ET patients (diagnosis period 1980-2010), followed in 11 Hematological Centers (universities 5, general hospitals 6) from the region Lazio in Central Italy. Median age at ET diagnosis is 62.5 years (range 17-93); 392 males, 634 females; median follow-up of the entire population is 6.2 years (range 0.1 – 31.9). Seventy/1026 patients (6.8%) developed 71 SM during follow-up. Observed SM were grouped as follows: genito-urinary 15, breast 14, non-melanoma skin cancer 12, lung 11, gastro-intestinal 8, hematologic 5, thyroid 3, central nervous system 1, soft tissue 1 and unknown 1.
Taking in consideration the different treatment approach, we divided our population in 5 different groups: group 0, no treated patients; group 1, patients treated either with Hydroxiurea (HU) alone or in combination/sequentially with Interpheron (IFN)/Anagrelide (ANA); group 2, patients treated either with alkylating agents (ALK) alone or in combination/sequentially with IFN/ANA; group 3, patients treated with ALK + HU sequentially; group 4, patients treated with ANA and/or IFN only. Characteristics of the patients are shown in the table.
| . | GROUP 0 NO THERAPY . | GROUP 1 HU . | GROUP 2 ALK . | GROUP 3 ALK + HU . | GROUP 4 ANA /IFN . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Secondary malignancy (SM) | Yes | No | Yes | No | Yes | No | Yes | No | Yes | No |
| Number (%) | 11 (5) | 209 | 46 (7.1) | 595 | 4 (15.4) | 22 | 8 (9.3) | 78 | 2 (3.8) | 51 |
| Gender(M/F) | 4/7 | 80/129 | 26/20 | 224/371 | 3/1 | 11/11 | 3/5 | 26/52 | 2/0 | 13/38 |
| Median age at ET diagnosis (years) | 67 (39-72) | 47 (17-83) | 69.5 (41-90) | 67 (21-96) | 63.5 (40-76) | 62 (33-85) | 61.5 (32-80) | 62 (31-85) | 63 | 34 (21-83) |
| Median period between ET diagnosis and treatment start (years) | NA | NA | 0.1 (0-11) | 0.2 (0-18) | 0.3 (0.1-6.6) | 0.2 (0-1.6) | 0.3 (0-1.6) | 0.2 (0-13) | 0 | 1.4 (0-10.2) |
| Median period between ET diagnosis and SM diagnosis (years) | 4.1 (0.7-15) | NA | 5.9 (0.2-22.4) | NA | 9.9 (3-28) | NA | 9.7 (1.6-21.3) | NA | 13.5 (9.1-17.9) | NA |
| Median period between treatment start and SM diagnosis (years) | NA | NA | 4.7 (0.1-22.4) | NA | 9.6 (2.9-21.5) | NA | 8.2 (1.6-21.3) | NA | 13.5 (9.1-17.9) | NA |
| Median period of drug exposure (years) | NA | NA | 5.6 (0.2-18.5) | 4.0 (0.1-30.4) | 5.5 (0.9-17) | 8.8 (0.4-23.4) | 14.7 (2.3-21) | 8.7 (0.6-24.2) | 13.3 | 3.1 (0.1-19.8) |
| . | GROUP 0 NO THERAPY . | GROUP 1 HU . | GROUP 2 ALK . | GROUP 3 ALK + HU . | GROUP 4 ANA /IFN . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Secondary malignancy (SM) | Yes | No | Yes | No | Yes | No | Yes | No | Yes | No |
| Number (%) | 11 (5) | 209 | 46 (7.1) | 595 | 4 (15.4) | 22 | 8 (9.3) | 78 | 2 (3.8) | 51 |
| Gender(M/F) | 4/7 | 80/129 | 26/20 | 224/371 | 3/1 | 11/11 | 3/5 | 26/52 | 2/0 | 13/38 |
| Median age at ET diagnosis (years) | 67 (39-72) | 47 (17-83) | 69.5 (41-90) | 67 (21-96) | 63.5 (40-76) | 62 (33-85) | 61.5 (32-80) | 62 (31-85) | 63 | 34 (21-83) |
| Median period between ET diagnosis and treatment start (years) | NA | NA | 0.1 (0-11) | 0.2 (0-18) | 0.3 (0.1-6.6) | 0.2 (0-1.6) | 0.3 (0-1.6) | 0.2 (0-13) | 0 | 1.4 (0-10.2) |
| Median period between ET diagnosis and SM diagnosis (years) | 4.1 (0.7-15) | NA | 5.9 (0.2-22.4) | NA | 9.9 (3-28) | NA | 9.7 (1.6-21.3) | NA | 13.5 (9.1-17.9) | NA |
| Median period between treatment start and SM diagnosis (years) | NA | NA | 4.7 (0.1-22.4) | NA | 9.6 (2.9-21.5) | NA | 8.2 (1.6-21.3) | NA | 13.5 (9.1-17.9) | NA |
| Median period of drug exposure (years) | NA | NA | 5.6 (0.2-18.5) | 4.0 (0.1-30.4) | 5.5 (0.9-17) | 8.8 (0.4-23.4) | 14.7 (2.3-21) | 8.7 (0.6-24.2) | 13.3 | 3.1 (0.1-19.8) |
NA: not applicable
Taking into account every single treatment group, although we observed an increased rate in the ALK one (4/26, 15.4%), we could not find a statistically significant difference in the risk of SM development. Instead, combining different groups we obtained the subsequent results: group 0 + 4 versus group 1, no statistically significant difference (p= 0.174); group 0 + 4 versus 2 + 3 statistically significant difference (p= 0.031). Compared to anagrelide, interferon or no treatment, alkylating agents alone or given sequentially with hydroxiurea, seem to increase the risk of SM development, while HU treatment alone do not.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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