Primary Plasma Cell Leukemia: Identity Card 2016.

Primary plasma cell leukemia (PPCL) is an aggressive and rare variant of multiple myeloma (MM), characterized by peculiar adverse clinical and biological features. Though the poor outcome of PPCL has been slightly improved by novel treatments during the last 10 years, due to the limited number of available studies in this uncommon disease, optimal therapy remains a classic unmet clinical need. Anyway, in the real-life practice, induction with a bortezomib-based three-drug combination, including dexamethasone and, possibly, lenalidomide, or, alternatively, thalidomide, cyclophosphamide, or doxorubicin, is a reasonable first-line option. This approach may be particularly advisable for patients with adverse cytogenetics, hyperleucocytosis, and rapidly progressive disease, in whom a fast response is required, or for those with suboptimal renal function, where, however, lenalidomide should be used with caution until renal activity is restored. In younger subjects, leukemia/lymphoma-like more intensive regimens, including hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone or continue-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide, may be also combined with bortezomib +/- thalidomide. Treatment must be started immediately after a diagnosis of PPCL is made to avoid the risk of irreversible disease complications and, in such a context, the prevention of tumor lysis syndrome is mandatory. In patients eligible for autologous stem cell transplantation (AuSCT), other alkylating agents, in particular melphalan, should be initially avoided in order to allow adequate collections of CD34+ peripheral blood stem cells (PBSC). A combination of lenalidomide and dexamethasone may be a valuable alternative option to manage older or unfit patients or those with slower disease evolution or with signs of neuropathy, contraindicating the use of bortezomib. Patients not suitable for transplant procedures should continue the treatment, if a response occurs and if tolerated, considering the possibility of a prolonged maintenance therapy. AuSCT should be pursued in all eligible patients less than 65 years old who achieve a significant response after a short course of induction treatment. PBSC collection should reach a threshold of at least 5 × 10(6) CD34+ PBSC/kg using cyclophosphamide plus G-CSF and adding the mobilizing agent plerixafor, if necessary. High-dose melphalan (HDM) (200 or 140 mg/m(2), according to age and renal function) remains the preferable conditioning regimen. A second AuSCT should be always considered, even in patients achieving complete response (CR) after the first AuSCT, as the short progression-free survival (PFS) generally seen in PPCL suggests the persistence of a relevant burden of residual disease; this provides a strong rationale for the use of post-transplantation therapies in PPCL to improve depth of response, to maintain remission, and, possibly, to increase survival, though consolidation and/or maintenance strategies with novel agents, whose efficacy has been well demonstrated in MM, have not been still extensively evaluated in PPCL. The search of a suitable donor should start as soon as possible and an allogeneic stem cell transplant (AlloSCT) with a myeloablative conditioning (MAC) regimen discussed with younger patients responsive to induction therapy and with poor prognostic parameters at diagnosis. A sequence of AuSCT followed by reduced intensity conditioning (RIC) or non-myeloablative (NMA) AlloSCT may be considered in selected cases. Salvage therapies for relapsed/refractory disease, especially using new drugs not employed at diagnosis, are sometimes effective in the short term, but a rapid relapse is still generally the rule; AlloSCT in relapsed and eligible patients with sensitive disease after salvage treatments is, therefore, recommended.