Maintenance of efficacy and its predictors after discontinuation of eltrombopag in adults with primary immune thrombocytopenia / 中华血液学杂志

Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.

Nilotinib treatment for imatinib resistant or intolerant chronic myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of nilotinib in chronic myelogenous leukemia (CML) patients with resistance or intolerance to imatinib.</p><p><b>METHODS</b>Thirty-five CML patients after imatinib failure or intolerance received oral administration of 400 mg nilotinib twice daily. The overall survival, hematologic and cytogenetic responses, as well as adverse events were evaluated.</p><p><b>RESULTS</b>The median duration of nilotinib therapy was 11 (1 - 23) months, with a median follow-up of 19 months. Nonhematologic adverse events were mostly of grade 1-2. The most common ones possibly related to nilotinib were increase of bilirubin (76%) and rash (46%). Grade 3-4 hematologic adverse events includes thrombocytopenia (37%), neutropenia (26%) and anemia (26%). Nilotinib was proved to be well-tolerated in this study. Grade 3-4 hematologic adverse events happened more frequently in advanced phase CML. The rate of major cytogenetic response in chronic phase (CP) CML was much higher than those in advanced CML (38.5% vs 22.2%). The median time to major cytogenetic response was 3 months. The estimated overall survival at 18 months was (93.5 +/- 1.0)%.</p><p><b>CONCLUSION</b>Nilotinib is a more effective and safe treatment option for imatinib-resistant or -intolerant CML-CP patients.</p>

Efficacy and safety of imatinib in treatment of 151 chronic myeloid leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of imatinib in treatment of chronic myeloid leukemia (CML) patients.</p><p><b>METHODS</b>From December 2003 to March 2007, 151 patients entered Glivec International Patient Assistance Program (GIPAP) in our center and received imatinib therapy. The overall and progression free survival, hematologic, cytogenetic and molecular response, and adverse events were evaluated. The factors associated with outcome of imatinib therapy were also analysed.</p><p><b>RESULTS</b>One hundred and forty-two patients were evaluable with a median follow-up duration of 21.5 (6 -78) months. (1) The rate of cumulative complete hematologic response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and complete molecular response (CMoR) in chronic phase (CP) CML patients were 96.9%, 82.6%, 76.1% and 29.4%, respectively. These rates were significantly higher in patients with CP than in those with accelerated phase (AP) and blast crisis (BC) (P < 0.0001). (2) The overall survival (OS) rates at 1, 2 and 3 year were 100%, (97.3 +/- 1.9)% and (95.8 +/- 2.4)% for CP patients, they were (84.7 +/- 8.2)%, (77.0 +/- 10.4)% and (69.3 +/- 11.9)% for AP patients, and (62.9 +/- 8.9)%, (41.9 +/- 9.2)% and (28.5 +/- 9.1)% for BC patients, respectively (P < 0.0001). The progression-free survival (PFS) rates at 1, 2 and 3 year were (98.9 +/- 1.1)%, (93.9 +/- 2.7)%, (93.9 +/- 2.7)% for CP patients, (68.9 +/- 10.6)%, (61.3 +/- 11.9)%, (61.3 +/- 11.9)% for AP patients, (36.4 +/- 8.8)%, (25.4 +/- 8.1)%, (10.1 +/- 8.2)% (P < 0.0001) for BC patients respectively. (3) Among 92 CP patients, the rates of MCyR and CCyR in newly diagnosed patients were significantly higher than those in interferon therapy failure patients (P = 0.015, P = 0.010). Patients obtained CCyR at 12 months after the initiation of imatinib treatment were associated with longer PFS (P = 0.0099). According to the Sokal scoring system, the rates of MCyR and CCyR in low-risk patients were significantly higher than those in intermediate-risk and high-risk patients (P = 0.0013, P = 0.0024). Sokal score was also significantly associated with disease progression (P = 0.0467). (4) The adverse events of imatinib were moderate and tolerable.</p><p><b>CONCLUSIONS</b>Treatment of CML patients in CP with imatinib can induce high hematologic, cytogenetic and molecular response and overall survival, but can not do satisfactorily for patients in AP and BC.</p>

Prognostic factors analysis for R-CHOP regimen therapy in diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To reassess the prognostic factors of diffuse large B cell lymphoma (DLBCL) treated with R-CHOP therapy.</p><p><b>METHODS</b>One hundred and twenty five patients were enrolled in this study from Feb. 2000 to Sep. 2006. They received 6 courses of R-CHOP regimen consisting of rituximab 375 mg/ m2, intravenously, d 1; cyclophosphamide 750 mg/m2, bolus intravenously, d 2; doxorubicin 50 mg/m2, bolus intravenously, d 2; vincristine 1.4 mg/m2, bolus intravenously, d 2 and prednisone 60 mg, orally, d 2 - 6. All the patients were evaluated and followed up after the treatment.</p><p><b>RESULTS</b>Eighty six patients (68.8%) achieved complete response (CR), 16 (12.8%) partial response (PR), 11 (12.8%) stable disease (SD) and 12 (9.6%) progressive disease (PD). In univariate analysis, performance status (PS), clinical stage, LDH level, extranodal disease, international prognostic index (IPI) and bulky disease were statistically significantly correlated with the induction of CR; however, only PS, clinical stage and bulky disease remained significant in multi-variate analysis (P = 0.0098, 0.000 and 0.004, respectively). Twenty four month for time to treatment failure (TTF) rate, overall survival (OS) rate, and disease free survival (DFS) rate was (59.7 +/- 5. 3)%, (67.1 +/- 5.6)% and (77.6 +/- 5.8)%, respectively. In univariate analysis, LDH, clinical stage and PS exerted significant effect on TTF and OS rate, but not on DFS rate; age and extranodal disease was not related with TTF, OS and DFS rate. In multi-variate analysis, achieved CR was the only prognostic factor for TTF (P =0.001) and bulky disease had influence on DFS rate. LDH level, PS, and achieved CR was correlated with the OS rate in multi-variate setting (P = 0.002, 0.009 and 0.001 respectively).</p><p><b>CONCLUSION</b>IPI score has its limitation in predicting the prognosis in the R-CHOP era in DLBCL. Other two relevant prognostic factors are bulky disease and achieved CR after 6 courses of treatment.</p>