Abstract
Background: Primary plasma cell leukemia (PPCL) is a rare and aggressive malignancy, with a peculiar clinical and biological features and very poor prognosis. It differs from secondary PCL (SPCL), a leukemic transformation from a previously diagnosed multiple myeloma (MM). Although a few studies have suggested that use of novel agents and performing autologous stem cell transplantation (ASCT) has prolonged survival time of PPCL patients, the prognosis is still poor compared with MM, and the optimal therapy remains unclear.
Materials and methods: 50 patients with PPCL were enrolled in Blood Diseases Hospital, Chinese Academy of Medical Sciences in China from June 1999 to June 2016. We analyzed the clinical and cytogenetic characteristics of these patients, survival analysis was conducted by Kaplan-Meier estimates and compared using the log-rank test.
Results: Median age of 50 cases was 58 years (range between 26 and 86 years), 76% patents were less than 60 years old. There were 34 males and 16 females. The most common immunoglobulin type was IgG (42%), 26% of patients had light chain type. Regarding the ISS, 2 (4.0%) patients were stage I, 7(14.0%) were stage II, and 41 (82.0%) were stage III. 44 patients (88%) was diagnosed with anemia, 5(10%)patients were found leukopenia, while 23 (46%) patients with leukocytosis. 38(76.0%) patients had thrombocytopenia at diagnosis. 14 (28%) patients were found with renal dysfunction. 42(84%) patients showed elevated LDH level.39 (78%) patients had high β-2microglobulin levels (> 5.5 mg/L). 20(40.0%) patients had low serum albumin levels (< 3.5 g/dL) . There were 33(66.0%) patients with hypercalcemia. Organomegaly (liver, spleen and etc.) was detected in 25 (50.0%) patients and osteolytic bone lesions were present in 34(68.0%) patients. 8(16.0%) patients were involved in extramedullary disease.
Cytogenetic analysis has showed that the most common abnormalities were complex karyotype (58.3%), while 50% patients with hypodiploid were found in 24 cases. FISH analysis showed that 13 patients with del13q, 15 patients with del17p, and 6 patients with t(4;14), while 12 patients with t(11;14). 14 patients were found at least 2 abnormalities of 30 patients.
All patients were treated in our hospital, 36 cases were treated with novel agent-based chemotherapy , such as bortezomib, cyclophosphamide, and dexamethasone(BCD), or bortezomib, doxorubicin, and dexamethasone (PAD), or thalidomide, melphalan, and prednisolone (MPT), or thalidomide ,cyclophosphamide, dexamethasone (TCD), or thalidomide and dexamethasone (TD), or bortezomib,dexamethasone,cis-platin,doxorubicin,cyclophosphamide,etoposide (VDPACE).8 patients were treated with conventional chemotherapy including vincristine, doxorubicin, and dexamethasone(VAD), or cyclophosphamide, etoposide, dexamethasone(CED), or melphalan and prednisolone(MP), or M2 regimen. 6patients received hematopoietic stem cell transplantation (HSCT) after initial induction chemotherapy, 4 of them received ASCT, 2 patients with allogeneic stem cell transplantation (allo-SCT).
Three patients achieved complete remission (CR), while 6 patients received very good partial remission (VGPR) after novel agent therapy. In the conventional chemotherapy group, only one patient received VGPR, and 3 patients received partial remission (PR). In the HSCT group, there were one with CR, and 2 patients with VGPR. Overall response rates (ORR) were significantly higher in patients with novel agent-based regimens compared with those treated with conventional chemotherapy (72% vs. 50%, P < 0.05). (Table 3)
Take the total cohort as a whole, the median PFS and OS were 6 months (95% CI 0-15.67), and 12 months (95% CI 5.08-18.09). In total, 5 (10%) patients died within less than 1 month. The major causes of early mortality were disease progression and infection. The median OS was lower in patients who were initially treated with conventional agents (12 months, 95%CI 0-26.4) compared with those treated with novel agents (24 months, 95% CI 8.9-39.5, P = 0.15), but the difference was not statistically significant. Additionally, patients with complex karyotypes showed a trend with poor survival compared to those with normal one.
Conclusion: Plasma cell leukemia has a higher incidence in cytogenetic aberrations. Novel agent-based chemotherapy combined with SCT could deepen the response rate, and improve the survival time.
No relevant conflicts of interest to declare.
