Abstract
Accelerated phase marks the onset of advanced rapidly progressive chronic myelogenous leukaemia (CML) and generally leads finally to a fatal blast crisis (BC) within 6 months.
Gleevec (imatinib mesylate) as a potent tyrosine kinase inhibitor has demonstrated significant activity in chronic phase (CP) of CML.
Because of the observed activity and favorable tolerability of Gleevec and because of the limited treatment options available to these patients we have introduced Gleevec in CML patients meeting rigorous criteria for acceleration and blast crisis phase of CML.
PATIENTS: MALE - 31 and FEMALE - 20 were eligible for inclusion in this study if they were at least 18 years old and had a diagnosis of Ph+ CML (AP; BC) confirmed by cytology, histology, cytogenetic and molecular analyses.
Characteristics CML patients (AP-accelerated phase; BC-blast crisis phase) is showed in table 1.
Table 1- Demographics, Disease History and Characteristics of CML Patients.
| 1 | ||
| Duration time of CML-yr | 3.8 (1–4.5) | 3.7 (0.7–5.1) |
| Prior therapy -n(%) | 100% | 100% |
| combined Chemotherapy | 10 (33) | 18 (86) |
| BMT | 2 (6.6) | 0 |
| Sokal’s score | ||
| >0.8 | 16 (53) | 15 (71) |
| PLT (x 109/L) | ||
| 100.0–300.0 | 11 (37) | 8 (38) |
| >300.0 | 15 (50) | 4 (19) |
| Blasts in peripheral blood (%) | ||
| median | 9 | 34 |
| range | 4–20 | 31–80 |
| Blasts in bone marrow (%) | ||
| range | 10–25 | 32–78 |
| HGB (g%) | ||
| median | 6.24 | 6.12 |
| range | 5.0–9.4 | 4.4–10.0 |
| Gleevec dosage | AP | BC |
| 300mg: n (%) | 1 (3.3) | 1 (4.8%) |
| 400 mg: n (%) | 4 (13.3) | 1 (4.8) |
| 600–800 mg: n (%) | 25 (83.4) | 19 (90.4) |
| Duration of treatment (months) | AP | BC |
| median | 31.64 | 40.0 |
| range | 1–98 | 0.5–91 |
| 1 | ||
| Duration time of CML-yr | 3.8 (1–4.5) | 3.7 (0.7–5.1) |
| Prior therapy -n(%) | 100% | 100% |
| combined Chemotherapy | 10 (33) | 18 (86) |
| BMT | 2 (6.6) | 0 |
| Sokal’s score | ||
| >0.8 | 16 (53) | 15 (71) |
| PLT (x 109/L) | ||
| 100.0–300.0 | 11 (37) | 8 (38) |
| >300.0 | 15 (50) | 4 (19) |
| Blasts in peripheral blood (%) | ||
| median | 9 | 34 |
| range | 4–20 | 31–80 |
| Blasts in bone marrow (%) | ||
| range | 10–25 | 32–78 |
| HGB (g%) | ||
| median | 6.24 | 6.12 |
| range | 5.0–9.4 | 4.4–10.0 |
| Gleevec dosage | AP | BC |
| 300mg: n (%) | 1 (3.3) | 1 (4.8%) |
| 400 mg: n (%) | 4 (13.3) | 1 (4.8) |
| 600–800 mg: n (%) | 25 (83.4) | 19 (90.4) |
| Duration of treatment (months) | AP | BC |
| median | 31.64 | 40.0 |
| range | 1–98 | 0.5–91 |
Patients received Gleevec 300–800 mg orally daily (table 2). Clinical evaluation of Gleevec therapy was determined by the rate of sustained haematological response (lasting >= 4 weeks)
The results of Gleevec therapy are showed in table 2.
Table 2 - Haematologic Response in Patients with AP & BC Phase after Gleevec Treatment
| Response . | AP . | BC . |
|---|---|---|
| 2 | ||
| CHR | 25 (83.3%) | 4 (19.0%) |
| Cytogenetic response | ||
| Major : | 5 (16.7%) | 1 (4.8%) |
| CCR | 2 (6.7%) | 0 |
| PCR | 3 (10.0%) | 1 (4.8%) |
| Minimal | 11 (36.7%) | 1.4.8%) |
| No response | 9 (30%) | 18 (85.6%) |
| BMT performed | 5 (16.7%) | 2 (9.6%) |
| after Gleevec therapy (months) | 6–12 | 7–13 |
| Response . | AP . | BC . |
|---|---|---|
| 2 | ||
| CHR | 25 (83.3%) | 4 (19.0%) |
| Cytogenetic response | ||
| Major : | 5 (16.7%) | 1 (4.8%) |
| CCR | 2 (6.7%) | 0 |
| PCR | 3 (10.0%) | 1 (4.8%) |
| Minimal | 11 (36.7%) | 1.4.8%) |
| No response | 9 (30%) | 18 (85.6%) |
| BMT performed | 5 (16.7%) | 2 (9.6%) |
| after Gleevec therapy (months) | 6–12 | 7–13 |
The most often observed side effects were irst few months ( neutropenia, thrombocytopenia, weakness, bone and muscles pain, headache, nausea, vomiting, diarrhoea, legs’ oedema, deaths (6.3% – 27.3%).
Conclusions:
Imatinib as a single agent is well tolerated and has substantial activity in the accelerated phase of CML.
The overall response rate in these cases was 83%. Imatinib as a single agent is well tolerated and has substantial activity in the accelerated phase of CML.
The overall response rate in these cases was 83%. Imatinib as a single agent is well tolerated and has substantial activity in the accelerated phase of CML.
The overall response rate in these cases was 83%.
5 pts. out of these 30 patients are still in the chronic phase after 10 to 32 months of follow-up.
In 4 ( 19%) out of 21 patients with BC the improvement after Gleevec therapy was short and transient mainly due to advanced stage of disease.
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