Plasma cell leukemia

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Plasma cell leukemia

Author: S Vincent Rajkumar, MD
Section Editor: Robert A Kyle, MD
Deputy Editor: Rebecca F Connor, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Dec 2021. | This topic last updated: Oct 08, 2020.

INTRODUCTION

Plasma cell leukemia (PCL) is a rare, yet aggressive form of multiple myeloma
characterized by high levels of plasma cells circulating in the peripheral blood. PCL can
either originate de novo (primary PCL) or as a secondary leukemic transformation of
multiple myeloma (secondary PCL).

The epidemiology, clinical presentation, diagnosis, prognosis, and treatment of plasma cell
leukemia are discussed here. The related disorders of multiple myeloma and
plasmacytoma are presented separately. (See "Multiple myeloma: Clinical features,
laboratory manifestations, and diagnosis" and "Diagnosis and management of solitary
extramedullary plasmacytoma" and "Diagnosis and management of solitary plasmacytoma
of bone".)

SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC

The coronavirus disease (2019) COVID-19 pandemic has increased the complexity of cancer
care. Important issues include balancing the risk from treatment delay versus harm from
COVID-19, ways to minimize negative impacts of social distancing during care delivery, and
appropriately and fairly allocating limited health care resources. These issues and
recommendations for cancer care during the COVID-19 pandemic are discussed separately.

● (See "COVID-19: Considerations in patients with cancer".)

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EPIDEMIOLOGY

PCL is a rare variant of multiple myeloma that presents either as a progression of

previously diagnosed multiple myeloma (ie, secondary PCL) or as the initial manifestation
of disease (ie, primary PCL). Historically, the majority of cases have been primary PCL (60 to
70 percent), although the incidence of secondary PCL may be increasing, perhaps due to
the longer survival of myeloma patients, such that the distribution of disease is more
evenly split [1,2].

The most extensive data on the epidemiology of PCL come from a series of 291 patients
identified in the Surveillance, Epidemiology and End Results (SEER) database between 1973
and 2004 [3]. During this period, approximately 49,000 patients with multiple myeloma
were identified, for a relative incidence of 0.6 percent. In this series there were no
significant differences based on gender, age, or race when compared with patients with
multiple myeloma. This SEER study did not distinguish between primary and secondary
PCL.

PCL occurs in all races and all geographic locations. The incidence of PCL in Europe is
approximately 4 cases per 10,000,000 persons per year [4]. As with multiple myeloma, PCL
is more common in Black Americans than in White populations [3].

Secondary PCL occurs as a progression of disease in 1 to 4 percent of all cases of multiple

myeloma [1,5,6]. Primary PCL presents at a slightly younger age with median ages at
diagnosis of 55 and 66 for patients with primary and secondary PCL, respectively.

CLINICAL PRESENTATION

Presenting signs and symptoms can include those seen in multiple myeloma (eg, renal
dysfunction, hypercalcemia, lytic bone lesions, bone pain, anemia) and in other leukemias
(eg, leukocytosis, anemia, thrombocytopenia, infections, hepatomegaly, splenomegaly).
Approximately 40 percent of patients will have already been diagnosed with multiple
myeloma [7].

As an example, a retrospective analysis reported the following clinical features in patients

presenting with PCL [1]:

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● Median white blood cell count – 18.6 cells/microL
● Median hemoglobin – 9.2 g/dL
● Median platelet count – 75 platelets/microL
● Osteolytic lesions – 44 percent
● Extramedullary plasmacytoma – 14 percent
● Hepatomegaly – 21 percent
● Splenomegaly – 13 percent

Other findings that may be present on physical examination include lymphadenopathy,

pulmonary findings related to pleural effusions, and neurological deficits due to central
nervous system involvement [2]. In addition, laboratory evaluation frequently
demonstrates elevated levels of lactate dehydrogenase (LDH) and beta-2 microglobulin.

PATHOLOGIC FEATURES

Peripheral blood

Morphology — The peripheral blood smear of patients with PCL demonstrates a

leukocytosis with circulating plasma cells. The absolute plasma cell count typically exceeds
2000/microL or 20 percent of the peripheral white blood cell count. (See 'Diagnosis' below.)

The morphological features of plasma cells can differ depending on their maturity and, at
times, may be indistinguishable from myeloblasts. Mature plasma cells are oval with
abundant basophilic cytoplasm (picture 1 and picture 2). The nucleus is round and
eccentrically located with a marked perinuclear hof, or cytoplasmic clearing. The nucleus
contains "clock-face" or "spoke wheel" chromatin without nucleoli. Immature plasma cells
have dispersed nuclear chromatin, prominent nucleoli and a high nuclear to cytoplasmic
ratio.

Immunophenotype — Immunohistochemistry or flow cytometry can be used to

determine the immunophenotype of the neoplastic plasma cells revealing a malignant
clone [8,9]. The cytoplasm of the neoplastic plasma cells contains either kappa or lambda
light chains, but not both, indicating that the cells are clonal. The neoplastic plasma cells
typically express CD138 and CD38. If present, CD45 is of low intensity. CD19 or CD20 are
usually absent. In contrast to most patients with multiple myeloma, the malignant cells in
PCL frequently lack CD56 expression.
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Genetic features — There is no single cytogenetic abnormality that is typical or

diagnostic of PCL. Hypodiploid or diploid cells are present in more than 80 percent of cases
[2]. The most common abnormalities are deletion of chromosome 13 and monosomy 13.
Deletion 17p, resulting in loss of TP53, has been detected in almost half of primary PCL and
three-quarters of secondary PCL. In addition, PCL frequently has abnormalities in
chromosome 1, in particular 1q21 amplification and del(1p21).

In one retrospective study, patients with PCL were noted to have the following high-risk
abnormalities [1]:

● Deletion of chromosome 13 by FISH in 67 to 85 percent

● t(4;14) in 16 percent
● t(14;16) in 16 percent
● del17p13 in 50 to 75 percent

This and other studies suggest that, when compared with multiple myeloma, PCL has a
higher incidence of t(11;14), t(14;16), and monosomy 13, with a similar incidence of t(4;14).

Bone marrow aspiration and biopsy — The findings on bone marrow aspiration and
biopsy are similar to those seen in multiple myeloma without PCL and demonstrate an
increased number of monoclonal plasma cells (picture 3). The bone marrow infiltration is
usually extensive and consists of plasma cells with a high proliferative index and anaplastic
or plasmablastic morphology [2].

Protein electrophoresis and immunofixation — Protein electrophoresis of the serum

and an aliquot from a 24-hour urine collection usually demonstrates monoclonal
immunoglobulin production (figure 1). (See "Laboratory methods for analyzing monoclonal
proteins", section on 'Serum protein electrophoresis (SPEP)'.)

Serum immunofixation will reveal production of one of the following immunoglobulins:

IgG, IgA, IgD, or IgE in 33, 20, 3, and 1 percent of cases, respectively (figure 2) [1].
Approximately 35 percent of patients will have light chain only disease and less than 10
percent will be non-secretors. (See "Laboratory methods for analyzing monoclonal
proteins", section on 'Serum immunofixation'.)

DIAGNOSTIC EVALUATION
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The diagnosis of PCL should be considered in patients with myeloma who present with or
develop circulating plasma cells on conventional leukocyte differential count/peripheral
smear evaluation and/or an elevated LDH, hepatosplenomegaly, or effusions. The
diagnostic evaluation of a patient with suspected PCL is identical to multiple myeloma, and
should include a review of the peripheral blood smear, bone marrow aspiration and biopsy,
serum protein electrophoresis with immunofixation, protein electrophoresis of an aliquot
from a 24-hour urine collection, and peripheral blood plasma cell assessment by flow
cytometry.

DIAGNOSIS

The diagnosis of PCL is based on an evaluation of the peripheral blood smear, bone
marrow aspiration and biopsy, and protein electrophoresis. The diagnosis is confirmed
when a monoclonal population of plasma cells is present in the peripheral blood with an
absolute plasma cell count exceeding 2000/microL or 20 percent of the peripheral blood
white cells [10-12]. These cutoffs are arbitrary, and PCL should be considered whenever
circulating plasma cells are readily detected on conventional complete blood count
evaluation, especially if they comprise 5 percent or more of the peripheral blood white cell
differential count. Repeat testing will usually clarify the diagnosis. Significant involvement
of the liver or pleural effusions with positive cytology for malignant plasma cells usually
suggests PCL.

The cytoplasm of the neoplastic plasma cells must contain either kappa or lambda light
chains, but not both, indicating that the cells are clonal.

Bone marrow aspiration and biopsy will demonstrate a monoclonal population of plasma
cells. Monoclonal protein on serum protein electrophoresis (SPEP) or urine protein
electrophoresis (UPEP) supports but is not necessary for making the diagnosis.

The criteria used to define PCL have not been validated prospectively and are under
investigation [2]. The original diagnostic criteria required both an absolute plasma cell
count exceeding 2000/microL and 20 percent of the peripheral blood white cells [10,12].
However, many of the published case series required only one of these criteria for the
diagnosis. There are concerns that these diagnostic criteria are not able to identify all
patients with PCL. As an example, heavily pretreated patients may have a significant

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leukopenia at baseline that may prevent them from reaching the absolute plasma cell
count criterion. In addition, the absolute number of plasma cells identified depends at
least somewhat on how aggressively the pathologist screens the peripheral blood smear to
identify circulating plasma cells. As such, studies have been proposed to investigate if
lower plasma cell levels (eg, 5 percent and/or absolute peripheral blood plasma cell count
≥0.5 x 109/L) have the same prognostic impact and whether flow cytometry should be used
to provide a less subjective measure of disease burden [2,13].

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of PCL includes other leukemias and lymphomas with abnormal
cells circulating in the peripheral blood. It also includes reactive polyclonal plasmacytosis
that can be related to infectious or autoimmune disorders.

The majority of cases will be easily distinguished from other forms of leukemia and
lymphoma by morphology with confirmation by flow cytometry or immunohistochemistry.
Patients with multiple myeloma or other plasma cell dyscrasias are arbitrarily
distinguished from PCL by lower numbers of circulating plasma cells, if present. A
diagnosis of reactive polyclonal plasmacytosis can be excluded based on absence of kappa
or lambda light chain restriction.

PROGNOSIS

The prognosis of PCL is poor; historically median survival was only 6 to 11 months, with up
to 28 percent dying within the first month after diagnosis [1,3,10,14]. Survival was even
shorter (two to seven months) when PCL (secondary) occurred in the context of refractory
or relapsed multiple myeloma [1]. While still suboptimal, overall survival has improved
modestly with the widespread use of high-dose therapy with autologous hematopoietic
cell transplantation (rescue) and the availability of novel agents. This was best illustrated in
an analysis of the Surveillance, Epidemiology, and End Results (SEER) database of 445
patients with primary PCL diagnosed between 1973 and 2009 which reported median
overall survival times of 5, 6, 4, and 12 months for those patients diagnosed during 1973-
1995, 1996-2000, 2001-2005, and 2006-2009, respectively [15].

It is likely that the reasons for poor outcome in PCL is related to a high proliferative rate
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and the fact that the malignant cells often harbor multiple cytogenetic abnormalities that
are known to be associated with rapidly progressive, or high risk, multiple myeloma. In one
retrospective study, patients with PCL were noted to have the following high-risk
abnormalities [1]:

● Deletion of chromosome 13 by FISH in 67 to 85 percent

● t(4;14) in 16 percent
● t(14;16) in 16 percent
● del17p13 in 50 to 75 percent

Genetic markers of high-risk myeloma are discussed in more detail separately. (See
"Multiple myeloma: Pathobiology", section on 'Cytogenetic abnormalities'.)

TREATMENT

Pretreatment evaluation — Because of the rigorous nature of the chemotherapy

required for the treatment of PCL, particular attention should be paid in the history and
physical examination to the presence of comorbid conditions in the patient that could
complicate overall management. The history should pay specific attention to complaints of
bone pain, constitutional symptoms, neurological symptoms, and infections. The physical
examination should include a detailed neurologic exam.

Our pretreatment evaluation also includes the following studies, some of which are
performed as part of the diagnostic evaluation:

● A complete blood count and differential with examination of the peripheral blood
smear. Flow cytometry of the peripheral blood.

● A chemistry screen that includes measurements of serum calcium, creatinine,

albumin, lactate dehydrogenase, uric acid, phosphorus, beta-2 microglobulin, and C-
reactive protein. (See "Multiple myeloma: Staging and prognostic studies".)

● Serum free monoclonal light chain (FLC) measurement.

● A serum protein electrophoresis (SPEP) with immunofixation and quantitation of

immunoglobulins. A routine urinalysis and a 24-hour urine collection for
electrophoresis (UPEP) and immunofixation. (See "Laboratory methods for analyzing
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monoclonal proteins".)

● Bone marrow aspiration and biopsy with immunophenotyping, conventional

cytogenetics, and fluorescence in situ hybridization (FISH). FISH should target
t(11;14), 1q+, and del17p.

● A metastatic bone survey with plain radiographs including the humeri and femoral
bones should be performed in all patients. If patients have a normal or indeterminate
bone survey in the setting of bone pain, or have neurological deficits that may be due
to spinal cord compression, additional imaging such as MRI, CT, or PET/CT should be
performed. MRI and PET/CT are useful in patients in whom there is uncertainty about
the extent of bone disease. PET/CT is also useful when there is any concern for the
presence of extramedullary disease. The role of these imaging modalities is evolving.

● A study of cardiac ejection fraction (eg, echocardiogram or MUGA) should be

performed for most patients.

Initial treatment — There have been no prospective randomized trials investigating the
treatment of PCL. Recommendations are primarily based on data from small retrospective
series, case reports, and extrapolation of data from patients with multiple myeloma. In
general, patients younger than 65 years in good performance status are treated with
aggressive induction therapy, such as VDT-PACE (bortezomib, dexamethasone,
thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) followed by
autologous hematopoietic cell transplantation (HCT) [16]. Eligibility for HCT is discussed
separately. Chemotherapy alone is the principal option for those ineligible for HCT. (See
"Determining eligibility for autologous hematopoietic cell transplantation".)

Given the high tumor burden and aggressiveness of the disease, patients with PCL are at
risk for developing tumor lysis syndrome. This syndrome is best prevented via appropriate
treatment with aggressive intravenous fluid hydration, prophylactic rasburicase or
allopurinol, correction of any prior electrolyte disturbances and elements of reversible
renal failure, as well as the provision of sufficient fluids to insure a high urine output.
Patients should be monitored with serum uric acid, calcium, phosphorus, and serum
creatinine (algorithm 1). This is most appropriately performed in a continuously monitored
inpatient setting. (See "Tumor lysis syndrome: Prevention and treatment".)

Induction therapy — The best induction regimen for PCL is not known and there is great
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variability in clinical practice. Historically, patients with PCL have had poor overall survival
with older treatments for multiple myeloma [1,17,18]. Lenalidomide- and bortezomib-
based regimens used now as front-line therapy for multiple myeloma have demonstrated
activity in PCL [19-23]. In particular, combinations that incorporate the proteasome
inhibitor bortezomib may be very active.

In our practice, for patients with PCL, we suggest induction therapy with a bortezomib-
based regimen, such as VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin,
doxorubicin, cyclophosphamide, and etoposide), VTD (bortezomib, thalidomide,
dexamethasone) (table 1), VRD (bortezomib, lenalidomide, dexamethasone) (table 2), or
VCD (bortezomib, cyclophosphamide, dexamethasone) (table 3) [24,25].

This suggestion is based on a desire to maximize the potential yet largely unknown
beneficial effects of bortezomib given the known poor outcome with other therapies. For
patients who are candidates for transplantation, we suggest proceeding after induction
therapy to high-dose therapy plus autologous HCT.

Support for this approach comes from prospective trials that suggest proteasome
inhibitors, such as bortezomib, are one of our most active therapies in patients with high-
risk multiple myeloma as defined by genetic abnormalities. Since patients with PCL often
demonstrate these same genetic abnormalities, bortezomib has been tested in PCL.

The following is a survey of studies that have investigated bortezomib in the treatment of
PCL:

● In a phase II trial, 40 patients with PCL underwent induction with four cycles of
bortezomib-based chemotherapy [21]. Bortezomib, dexamethasone, and doxorubicin
(PAD) was given for cycles 1 and 3, and VCD was given for cycles 2 and 4. Responding
patients underwent high-dose melphalan plus autologous HCT followed by either a
second autologous HCT and maintenance therapy or a reduced intensity allogeneic
HCT. The overall response rate was 69 percent (10 percent complete). Median
progression-free and overall survivals were 15 and 36 months, respectively.

● A multicenter retrospective study of 73 patients with PCL included 14 patients initially

treated with a regimen that contained bortezomib [7]. Of these, 10 (71 percent)
demonstrated an at least partial response (four complete responses). Among patients
initially treated with bortezomib, thalidomide, or a combination of the two drugs, the
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median survival was 12.6 months, but among patients responding to bortezomib,
approximately half were alive without relapse at 26 months from diagnosis. In this
study, the choice of initial therapy did not affect survival, but the sample size does not
permit adequate comparisons, and no conclusions can be made.

● In another multicenter retrospective study of 42 patients with primary or secondary

PCL, bortezomib-based therapy was associated with higher response rates (69 versus
31 percent) and longer median survival (13 versus 2 months) [26]. When treated with
a bortezomib-based therapy, the median survival times of patients with primary and
secondary PCL were 18 and 7 months, respectively.

The above reports and smaller case reports show the safety and feasibility of bortezomib-
based initial therapy [23,27-36].

Transplantation — High-dose chemotherapy followed by autologous HCT results in

superior overall survival in patients with multiple myeloma and has become part of the
standard of care for eligible patients. The role of HCT in PCL is less clear. Prospective
randomized trials of HCT have not included patients with PCL. Case reports and case series
have recorded some long-term responses to autologous or allogeneic HCT in PCL [7,21,37-
40]. However, most of these data are based on patients who were treated with non-
bortezomib-based induction regimens.

Due to the poor prognosis with chemotherapy alone in these patients, we offer high-dose
chemotherapy followed by autologous stem cell rescue to eligible patients with PCL. This
approach follows bortezomib-based induction therapy as discussed above. Following HCT,
consideration should be given to some form of maintenance therapy to prevent relapse.
(See 'Induction therapy' above.)

The following is a compilation of reports on the use of HCT in PCL:

● The largest retrospective study was conducted by the European Group for Blood and
Marrow Transplantation and included 272 patients with primary PCL and 20,844
patients with multiple myeloma who had undergone autologous HCT from 1980 to
2006 [41]. While patients with PCL were more likely to enter complete remission after
transplantation, their median progression-free survival (14 versus 27 months) and
overall survival (26 versus 62 months) were inferior to that of patients with multiple
myeloma.
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● A retrospective study from the Center for International Blood and Marrow Transplant
Research analyzed the outcomes of patients with PCL who underwent autologous (97
patients, median age 56 years) or allogeneic (50 patients, median age 48 years) HCT
within 18 months of diagnosis between 1995 and 2006 [39]. Following autologous
HCT, estimated rates of progression-free survival, relapse, non-relapse mortality, and
overall survival at three years were 34, 61, 5, and 64 percent, respectively.
Corresponding rates following allogeneic HCT were 20, 38, 41, and 39 percent,
respectively, indicating inferior outcome with allogeneic compared with autologous
transplantation in this patient population.

● A multicenter retrospective analysis of 73 patients with primary PCL included 23

patients who had undergone a single autologous HCT (nine patients), a double
autologous HCT (eight patients), an allogeneic HCT (two patients) or a tandem
autologous/allogeneic HCT (four patients) [7]. Among patients who underwent HCT,
the median overall survival and duration of response were 38 and 27 months,
respectively. In this highly selected group, patients who survived initial therapy and
received HCT had superior survival and response durations when compared with
those who did not receive HCT.

● In a phase II trial of 40 patients with PCL treated with bortezomib-based induction,

responding patients underwent autologous HCT followed by either a second
autologous HCT (6 patients) or reduced intensity allogeneic HCT (16 patients) [21]. For
the entire cohort, median progression-free and overall survivals were 15 and 36
months, respectively. The median overall survival was not reached for those
undergoing autologous HCT and was 36 months for those undergoing allogeneic
HCT. Part of this survival benefit may reflect selection bias with younger patients who
survived initial therapy proceeding to HCT.

At present, the data above suggest that HCT may be of value in PCL, although no definite
conclusions can be made due to lack of randomized data. Further, there are no data on
whether allogeneic approaches offer any additional benefit compared with autologous
HCT.

Maintenance — Maintenance therapy refers to the prolonged administration of agents

with low toxicity profiles in an attempt to prevent progression of disease. There have been
no randomized studies of maintenance therapy in patients with PCL. However, since

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virtually all patients with PCL who attain a complete remission develop relapsed disease,
consideration should be given to some form of maintenance therapy. Maintenance therapy
can prolong progression-free survival in patients with multiple myeloma. The benefits of
improved progression-free survival must be balanced against an increased rate of severe
(grade 3/4) neutropenia, risk of second cancers and other toxicities, the cost, and the
possibility that the progression-free survival advantage may be neutralized by the use of
lenalidomide at time of first relapse.

However, given the short remission durations (14 months) seen in these patients and the
relatively mild toxicity of maintenance, we suggest the use of maintenance lenalidomide
and/or bortezomib rather than observation until relapse. Studies evaluating the use of
maintenance therapy after autologous transplantation in patients with multiple myeloma
are presented separately. (See "Multiple myeloma: Use of autologous hematopoietic cell
transplantation", section on 'Standard-risk disease'.)

Response assessment — Patients should be evaluated before each treatment cycle to

determine how their disease is responding to therapy. Response criteria that incorporate
response features used for acute leukemia and for multiple myeloma have been proposed
by the International Myeloma Working Group (table 4). This assessment includes the
following:

● Quantitation of peripheral blood plasma cells by morphologic review of the

peripheral smear

● Measurement of monoclonal (M) protein in the serum and urine (SPEP, UPEP)

● Evaluation of previously identified or suspected extramedullary disease

● Bone marrow evaluation is incorporated to identify very good partial response or

better

● The free light chain (FLC) assay and flow cytometry of the peripheral blood are
incorporated to identify stringent complete remission

The goal of therapy in PCL is to achieve and maintain a complete response, as much as
possible; this goal therefore influences the choice of the initial treatment options. However,
since the disease is not considered curable, failure to achieve a complete response should
not be construed as a reason to change or intensify therapy. There are no data that such
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an approach leads to superior survival. In selected patients with good performance status
who fail to achieve complete response, after a full discussion of the pros and cons,
consideration can be given to allogeneic hematopoietic cell transplantation and other
options used for patients with relapsed refractory disease. (See "Multiple myeloma: Use of
allogeneic hematopoietic cell transplantation".)

Relapse from complete remission is identified by the reappearance of a monoclonal

protein, the development of extramedullary disease, reappearance of circulating plasma
cells, or an increase in the bone marrow plasma cells to >10 percent [2]. Therapy should be
reinstated at the time of relapse.

Treatment of recurrent or refractory disease — There is little information on the

treatment of recurrent or refractory PCL. Patients who are eligible may be considered for
allogeneic HCT, or an autologous HCT followed by an allogeneic HCT. A trial of one or more
regimens active in myeloma that the patient has not been exposed to earlier is another
option. Regimens that have worked earlier in the same patient can be tried again if the
relapse occurred off-therapy. Patients who have undergone allogeneic HCT may respond
to withdrawal of immunosuppression or immunotherapy with donor lymphocyte infusion
(DLI).

Often there is no better therapy to offer a patient than enrollment onto a well-designed,
scientifically valid, peer-reviewed clinical trial. Additional information and instructions for
referring a patient to an appropriate research center can be obtained from the United
States National Institutes of Health (www.clinicaltrials.gov).

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Multiple
myeloma".)

SUMMARY AND RECOMMENDATIONS

● Plasma cell leukemia (PCL) is a rare, yet aggressive variant of multiple myeloma
characterized by high levels of plasma cells circulating in the peripheral blood. PCL
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can either originate de novo (primary PCL) or as a secondary leukemic transformation

of multiple myeloma (secondary PCL). (See 'Introduction' above.)

● Presenting signs and symptoms can include those seen in multiple myeloma (eg,
renal dysfunction, hypercalcemia, lytic bone lesions, anemia) and in other leukemias
(eg, anemia, thrombocytopenia, infections, hepatomegaly, splenomegaly). (See
'Clinical presentation' above.)

● The diagnostic evaluation of a patient with suspected PCL is identical to multiple

myeloma and should include a review of the peripheral blood smear, bone marrow
aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation,
and protein electrophoresis of an aliquot from a 24-hour urine collection (UPEP). (See
'Pathologic features' above.)

● The diagnosis is made when a monoclonal population of plasma cells is present in the
peripheral blood typically with an absolute plasma cell count exceeding 2000/microL
or 20 percent of the peripheral blood white cells. (See 'Diagnosis' above and
'Differential diagnosis' above.)

● The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is

even shorter (two to seven months) when PCL occurs in the context of refractory or
relapsing multiple myeloma. Survival may have improved with incorporation of new
agents into the treatment strategy. (See 'Prognosis' above.)

● There have been no prospective randomized trials investigating the treatment of PCL.
Recommendations are based primarily on data from small retrospective series, case
reports, and extrapolation of data from patients with multiple myeloma. In general,
patients are treated with induction therapy followed by hematopoietic cell
transplantation (HCT) in those who are appropriate candidates for this approach. (See
'Treatment' above.)

● The best induction regimen for PCL is not known and there is great variability in
clinical practice. For patients with PCL we suggest induction therapy with a
bortezomib-based regimen, such as VDT-PACE (bortezomib, dexamethasone,
thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) (Grade 2B).
(See 'Induction therapy' above.)

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● For patients who are candidates for transplantation, we suggest proceeding after
induction therapy to high-dose therapy plus autologous HCT (Grade 2C). (See
'Transplantation' above.)

● For most patients, we suggest the use of maintenance lenalidomide rather than
observation until relapse (Grade 2C). (See 'Maintenance' above.)

● There is little information on the treatment of recurrent or refractory PCL. Regimens

that have worked earlier in the same patient can be tried again if the relapse
occurred off-therapy. Allogeneic transplantation may be an option in eligible patients.
(See 'Treatment of recurrent or refractory disease' above.)

REFERENCES

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plasma cell leukemia. Leukemia 2008; 22:1044.
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statement on diagnostic requirements, response criteria and treatment
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bone marrow reactive plasmacytoses. Pathol Oncol Res 2009; 15:25.

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