Plasma cell leukemia is a rare malignancy with an aggressive clinical course and grave prognosis. Limited data on therapeutic outcomes and the absence of randomized data makes treatment decisions difficult in this disorder. This study of 147 patients is among the largest series of patients with pPCL and defines the outcomes after HCT in this disease.
In a recent study, 291 patients with PCL were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 1973-2004 (10
). The study did not distinguish between primary and secondary PCL. The median OS was 4 months and the median disease-specific survival was 6 months for patients with PCL; the 1-year, 2-year, and 5-year OS rates were 27.8%, 14.1%, and 6.4%, respectively. The median age was 67 years (range, 19-98 years) which is older than the median age of patients in our series. There is an inherent selection bias in a retrospective transplant series such as ours reflecting selection of patients who are younger, with better performance status and those surviving induction therapy, clinically improving on initial induction treatment and thus able to proceed to HCT.
In view of the aggressive course of plasma cell leukemia, the need for treatment with a relatively early and sustained response is desirable. The use of high dose melphalan in multiple myeloma was followed soon after with its use in plasma cell leukemia (11
). Allogeneic HCT has also been explored in this disease given the potential of a graft versus tumor effect. However, there is paucity of data reflecting the benefit of either approach in this disease (12
). Even with the caveat of patient selection bias, our data represent the highest quality evidence available regarding the role of HCT in pPCL. These data indicate that there is a significant subset patients for whom autologous HCT results in significant disease control and survival.
An analysis of the European Group for Blood and Marrow Transplantation (EBMT) reported outcomes after autologous HCT for patients with pPCL (13
). The EBMT study included patients reported to the registry with limited report forms regardless of complete data from 1980 onwards and excluded those receiving allogeneic HCT. In contrast to our results, the EBMT study demonstrated inferior post HCT survival in pPCL compared with MM. The limited data and the differing years of HCTfor the EBMT cohortmake direct comparisons difficult. Our analysis was restricted to those receiving HCT after 1995 (with >60% transplanted after 2000) and HCT early in the disease coursemaking it more applicable to current practices. This may account for the relatively superior results for this cohort compared to the EBMT data.
In our analysis, for those patients with pPCL able to receive a consolidativeautologous HCT within 18 mo of diagnosis, the PFS and OS were broadly similar to a cohort of MM patients receiving autologous HCT during the same time frame. However, during the same time period, 8% of patients with MM reported to the CIBMTR underwent an allogeneic HCT compared with 32% patients in our series with pPCL. This likely reflects a practice bias favoring the use of allogeneic HCT in pPCL based on its predicted aggressive biologic behavior. The median time from diagnosis to transplant was similar in the autologous and allogeneic HCT group. Our data indicates that although relapse rates are lower, allogeneic HCT carries a much higher risk of NRM and lower OS and PFS. The advent of NMA/RIC has not significantly changed overall outcomes compared with myeloablative conditioning in our cohort of allogeneic HCT recipients.
Despite a significant number of patients in our series undergoing HCT after 2000, few patients received novel agents (thalidomide, lenalidomide or bortezomib) as part of their induction regimen. Introduction of novel agents have been associated with an improvement in outcomes in multiple myeloma and in case reports of patients with PCL (14
). Emerging data in MM indicates improved PFS in patients who receive maintenance treatment post autologous HCT (18
). It is unclear from our database if patients received planned maintenance treatment and if so the nature of the treatment. Median PFS and OS was similar in the patients who underwent autologous HCT prior to and after 2000.
One possible explanation for the poor outcome of patients with PCL is that many harbor multiple cytogenetic abnormalities that are known to be associated with rapidly progressive disease or high risk multiple myeloma. In one retrospective study, patients with PCL were noted to have deletion of chromosome 13 by FISH in 67 to 85 percent, t(4;14) in 16 percent, t(14;16) in 16 percent and del 17q13 in 50 to 75 percent (3
). In our series, data on cytogenetics when available reflected known patterns.
This study is among the largest published experience on HCT for pPCL and confirms that autologous HCT is a safe and reasonable consolidative treatment option. Notably, the vast majority of patients (75%) were in complete or partial remission despite the majority not receiving novel agent induction. It is likely that autologous HCT was offered to patients with chemotherapy sensitive disease thus explaining the excellent outcomes after HCT in this report. Compared to MM, allogeneic HCT seems to be offered at a higher rate in clinical practice but was associated with a higher NRM and inferior outcomes compared with MM patients receiving allografts. In the absence of a defined standard of care, these data indicating similar outcomes and safety for HCT in pPCL sensitive to induction therapy, it is reasonable to consider transplant options similar to high risk MM for this disease. Those with excellent responses to induction therapy may represent a subgroup likely to benefit from autologous HCT.
Progress in the study of a rare disease like pPCL will be facilitated by collaborations between centers with consensus protocols that incorporate appropriate randomization strategies and correlative studies to better understand the biology of the disease. Clinical trials aimed at reducing relapse after autologous HCT, by incorporating the newer agents as part of induction and as maintenance therapy are needed. Ongoing efforts to reduce NRM after allogeneic HCT may result in improved outcomes with this modality in the future.