Canterbury DHB

Plasma Cell Leukaemia

This is a rare disorder making up about 2% of myeloma type presentations. The WHO criteria require >2x10e9/L circulating plasma cells or >20% total white cell count for a diagnosis of Plasma Cell Leukaemia (PCL). When noted at first presentation it is termed Primary PCL but when seen as a transforming event during treatment of myeloma it is deemed secondary PCL.

This is an aggressive disease with short survival. As it is rare, treatment strategies are based on expert opinion, small case series, case reports and retrospective analyses. Overall, treatment is extrapolated from strategies used for myeloma but opinion favours a much more aggressive approach with treatment intensity akin to that for acute leukaemia rather than myeloma.

About one case per year is reported in New Zealand.

No treatment has been shown to be superior when measured using overall survival. However, some approaches give a higher initial response rate and this is potentially of use if looking at intensification with auto SCT and RIC allo SCT or even “time without treatment”. Expert opinion supports an intensive approach to this disorder with treatment intensity akin to that used for acute leukaemia.

Basic therapy with melphalan and prednisone does not appear to be as effective as combination chemotherapy with VCMP/VABP (alternating vinc/cyclo/mel/pred with vinc/bleo/adria/pred)1 or as effective as either VAD or cyclo-etoposide (cyclo 600mg/m2/d x5d + etoposide 180mg/m2/d x5d q4w)2. The latter 2 protocols allow for stem cell mobilisation down the line. Hyper-CVAD has also been used for induction3.

3. Saccaro S, Fonseca R, Veillon DM, Cotelingam J, Nordberg ML, Bredeson C, Glass J, Munker R, Saccaro S, Fonseca R and others. Primary plasma cell leukemia: report of 17 new cases treated with autologous or allogeneic stem-cell transplantation and review of the literature. American Journal of Hematology 2005;78:288-94.

2. Dimopoulos MA, Palumbo A, Delasalle KB, Alexanian R. Primary plasma cell leukaemia. Br J Haematol 1994;88:754-9.

1. Garcia-Sanz R, Orfao A, Gonzalez M, Tabernero MD, Blade J, Moro MJ, Fernandez-Calvo J, Sanz MA, Perez-Simon JA, Rasillo A and others. Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. Blood 1999;93:1032-7.

Thalidomide has shown efficacy in PCL both as initial therapy and in the relapsed/refractory situation4. Most reports have used thal as a single agent or with dexamethasone but thal could instead be incorporated with chemotherapy such as with cyclo-dex or cyclo-Etop-dex5. DT-PACE (Dexamethasone, Thalidomide, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide) is an alternative.

5. Moehler TM, Neben K, Benner A, Egerer G, Krasniqi F, Ho AD, Goldschmidt H. Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 2001;98:3846-8.

4. Gertz MA, Gertz MA. Managing plasma cell leukemia.[comment]. Leukemia & Lymphoma 2007;48:5-6.

Lenalidomide use has been reported in 2 patients in combination with dexamethasone and has given responses6. Dose example 25mg/d d1=21 q4w.

6. Benson DM, Jr., Smith MK, Benson DM, Jr., Smith MK. Effectiveness of lenalidomide (Revlimid) for the treatment of plasma cell leukemia.[comment]. Leukemia & Lymphoma 2007;48:1423-5.

Bortezomib has also shown efficacy in PCL. In the largest series of 12 patients7, bortezomib was either used alone, with dexamethasone, with doxorubicin+dexamethasone, with thalidomide or with Thal-dex. The patients were first line, second line or above. The Bortezomib-doxorubicin-dexamethasone combination allowed for successful stem cell harvest down the line. Dose example, bortezomib 1.3 mg/m2 d1,4,8,11 q21d. Bortezomib has been combined with thalidomide, cyclophosphamide and dexamethsone. As well as DT-PACE in “Total Therapy 3”8

8. van Rhee F, Bolejack V, Hollmig K, Pineda-Roman M, Anaissie E, Epstein J, Shaughnessy JD, Jr., Zangari M, Tricot G, Mohiuddin A and others. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. 2007. p 827-832.

7. Pellegrino Musto FRFGVPTGGDAFFNFRGAPftGGaGCGI. Efficacy and safety of bortezomib in patients with plasma cell leukemia. 2007. p 2285-2290.

Autologous SCT is recommended for PCL 3,9 although no randomised comparison has been made. One patient is reported in CR at 89 months post auto.

9. Hovenga S, de Wolf JT, Klip H, Vellenga E. Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses: a report of three cases and a review of the literature. Bone Marrow Transplant 1997;20:901-4.

Allogeneic SCT is reviewed by Saccaro et al3. Of the few patients reported, some have early relapse post transplant but it is not clear if any achieve long term disease control. One patient is reported in PR 47 months post allo. From the 9 PCL patients treated with an allo, 7 died; 1 from aGvHD, 2 from infection, 3 from relapse and 1 unknown. A further case report describes a patient in CR 13 months after the allo SCT10

10. Nonami A, Miyamoto T, Kuroiwa M, Kunisaki Y, Kamezaki K, Takenaka K, Harada N, Teshima T, Harada M, Nagafuji K and others. Successful treatment of primary plasma cell leukaemia by allogeneic stem cell transplantation from haploidentical sibling. Japanese Journal of Clinical Oncology 2007;37:969-72.

No RIC allogeneic transplants have been reported.

Topic Code: 6777