Plasma cell leukemia

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Plasma cell leukemia
A schematic showing peripheral blood with plasma cell leukemia. Many plasma cells are seen mixed with red cells.
SpecialtyHematology and oncology

Plasma cell leukemia (PCL) is a

plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.[1][2]

Signs and symptoms

Primary PCL

The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in

hypercalcemic crisis, i.e. a potentially life-threatening episode of high ionic calcium (Ca2+) levels in the blood due to excess bone re-absorption and/or renal failure; b) higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.[1][4]

Secondary PCL

Secondary PCL (sPCL) is diagnosed in 1-4% of patients known to have had multiple myeloma for a median time of ~21 months. It is the terminal phase of these patients myeloma disease. sPCL patients typically are highly symptomatic due to extensive disease with malignant plasma cell infiltrations in, and failures of, not only the bone marrow but also other organs. They have failed or broken through one or more treatment regimens and therefore may also show some of the toxic effects of these treatments.[1][5]

Cause

PCL is caused by the development of an excessively high number of genetic abnormalities in plasma cells or, more particularly, their precursor B cells and plasmablasts (see

gene promotors and various less direct effects. These genetic abnormalities effect the Wnt signaling pathway, regulation of the cell cycle, RNA metabolism, protein folding, and cadherin-related cell adherence to extracellular matrix. These effects in turn control plasma cell proliferation, survival, apoptosis, adhesion to bone marrow, genome stability, and secretion of monoclonal immunoglobulins.[6]

Secondary plasma cell leukemia (sPCL) results from the comparatively slow development of plasma cell/plasma cell precursor genetic abnormalities which initially create a clone of cells that cause the

CD56 antigen which is present on the majority of plasma cells taken form multiple myeloma patients; and pPCL plasma cells more frequently express CD28 than do sPCL plasma cells. Thus, immunophenotyping supports that notion that multiple myeloma, sPCL, and pPCL show critically important fundamental differences that may explain their different clinical presentations, courses, responses to therapy, and prognoses.[6][8][9][10]

Diagnosis

The

CD45+/- phenotype) may be a more sensitive method to enumerate circulating clonal plasma cells and diagnose plasma cell leukemia.[3]

Treatments

Prior to the use of newly developed drugs and treatment regimens, median survival rates from the time of diagnosis for pPCL and sPCL were 8–11 months and 2–8 months, respectively, even when treated very aggressively with the VAD regimen of vincristine, doxorubicin, and dexamethasone or the VCMP regimen of vincristine, carmustine, melphalan, and prednisone alternating with vincristine, carmustine, doxorubicin, and prednisone.[1][5] The treatment of PCL patients, particularly pPCL patients, with newer methods appears to have made modest improvements in survival rates. However, the rarity of these two leukemias has limited individual studies to case reports on a small number of patients or retrospective analyses of patient records. Randomized controlled trials on these patients have not been reported. One flaw of these methods is patient selection bias, i.e. patients selected for treatment with a new regimen may be less ill than average patients with the disease and therefore have an intrinsically less aggressive (i.e. longer overall survival time) disease.[4]

Primary plasma cell leukemia

Recent case report studies suggest that treatment regimens which include a

immunosuppressant related to thalidomide), bortezomib, and dexamethasone (a corticosteroid) has a progression free survival rate of 66% at 3 years and an overall survival rate of 73% at 4 years. In one study, patients receiving intensive chemotherapy plus autologous stem-cell transplantation had a median survival of 34 months while those receiving chemotherapy alone had a median survival of 11 months. Two other studies that included bortezomib in their chemotherapy regimens likewise found that the addition of autologous stem-cell transplantation improved results. Current recommendations for treating pPCL often include induction with a three drug regimen such as borezomib-lenalidomide-dexamethasone followed by autologous stem-cell transplantion and consolidation/maintenance with of combination of immunomodulator agents (e.g. thalidomide, lenalidomide, or pomalidomide) plus a proteasome inhibitor (bortezomib, ixazomib, or carfilzomib.[4][10][11]

Secondary plasma cell leukemia

As the end stage of multiple myeloma that has failed or broken through one or more therapeutic regimens, sPCL continues to be highly refractory to various treatment regimens (<50%), very short response times of these regiments, and poor overall survival rates (median survival of 2–8 to months).[1][5][12] Patients with sPCL may have short-lived responses to treatment regimens (as communicated in case reports) that include bortezomid but there are no established therapeutic regimens that have clearly been shown to improve their overall or median survival.[4][10]

See also

References

  1. ^
    PMID 23288300
    .
  2. ^
    PMID 28255016
    .
  3. ^ a b Gonsalves, Wilson I. (2017-04-10). "Primary Plasma Cell Leukemia: A Practical Approach to Diagnosis and Clinical Management". American Journal of Hematology / Oncology. 13 (3).
  4. ^
    S2CID 22803869
    .
  5. ^
    PMID 23303035
    .
  6. ^
    PMID 26046463
    .
  7. PMID 28466550
    .
  8. ^
    S2CID 3292996
    .
  9. PMID 9626472
    .
  10. ^
    PMID 25778450
    .
  11. PMID 24957143
    .
  12. PMID 27104188
    .
Bibliography
  • Greer JP, Foerster J, and Lukens JN, "Wintrobe's Clinical Hematology", Lippincott Williams & Wilkins 11th ed., 2003.
  • Hoffman R, Benz E, Shattil S, Furie B, Cohen H, "Hematology: Basic Principles and Practice", Churchill Livingstone, 4th ed, 2004.
  • Hoffbrand AV, Catovsky D, and Tuddenham E, "Postgraduate Haematology", Blackwell, 5th ed., 2005.
  • Hoffbrand AV, Moss PAH, and Pettit JE, "Essential Haematology", Blackwell, 5th ed., 2006.

External links

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