plasma cell leukemia ( pcl ) is a rare disease that represents approximately 4% of plasma cell malignant disorders.1 diagnosis of pcl is established based on kyle s criteria , which includes an absolute plasma cell number accounting for greater than 2000/l or 20% of white blood cell differentiation.2 pcl consists of two variants : primary pcl presents in patients with no previous history of multiple myeloma ( mm ) , while secondary pcl consists of a leukemic transformation in previously recognized mm.3 primary pcl is an extremely resistant , rapidly progressive , fatal disease , with a median overall survival of 6.8 months.4 there is no standard therapeutic strategy because none of the treatment options have been prospectively evaluated .
we describe herein a successful case of newly diagnosed primary pcl , treated with a regimen that included bortezomib , followed by auto stem cell transplantation ( asct ) and nonmyeloablative allogeneic stem cell transplantation ( allo - sct ) .
a 37-year - old man with suspected primary pcl was sent from a nearby hospital to our institution in february 2010 .
table 1 shows the laboratory data of the initial medical examination , and table 2 shows the data on admission to our hospital . the white blood cell count and its differentiation met kyle s criteria .
the patient had acute heart failure . his chest x - ray revealed cardiomegaly ( cardiothoracic ratio was 59% ) with slight pulmonary congestion .
amino - terminal pro - brain natriuretic peptide levels were elevated to 811.2 pg / ml .
this acute heart failure was probably caused by cardiac amyloidosis , as cardiac ultrasound showed a granular sparkling pattern .
these cells were negative for cyclin d1 , cd3 , cd5 , cd10 , cd20 , cd56 , cd79a , and  chain , and positive for cd138 and  chain .
no immunoglobulin h / cyclin d1 ( igh / bcl1 ) translocations were found in fluorescence in situ hybridization analysis .
treatment with a pad regimen ( bortezomib 1.3 mg / m [ days 1 , 4 , 8 , and 11 ] , adriamycin 1.3 mg / m [ days 1 , 4 , 8 , and 11 ] , and dexamethasone 40 mg / body [ days 14 , 811 , and 1518 ] ) was started .
as soon as the treatment was started , leukemic plasma cell levels rapidly decreased ( figure 1 ) .
no organ dysfunction was detected , except that serum creatinine levels temporarily increased to 1.21 mg / dl . on day 27 of the first pad cycle
after three pad cycles , we were unable to assess his bone marrow , because it remained dry tap .
serum / , a surrogate marker for the treatment effect of this case , became similar to normal levels .
in addition , the granular sparkling pattern detected by cardiac ultrasound at the time of admission disappeared . the patient was then administered high - dose therapy ( hdt ) + asct . before hdt + asct , his p eripheral blood stem cells containing 10.9  10/kg cd34-positive cells were harvested with high - dose cyclophosphamide .
he received hdt + asct with a conditioning regimen of high - dose melphalan ( 100 mg / m [ days 3 and 2 ] ) and bortezomib ( 1 mg / m [ days 7 , 4 , + 1 , and + 4 ] ) . at the end of hdt + asct
sixty - seven days after hdt + asct , the patient received allogeneic bone marrow stem cell transplantation ( allo - bmt ) from his human leukocyte antigen - matched brother , containing 2.1  10/pt kg nuclear cells and 1.44  10/pt kg cd34-positive cells .
the conditioning regimen consisted of fludarabine ( 30 mg / m [ day 6 to day 2 ] ) and total body irradiation ( 2 gy [ day 1 ] ) .
graft - versus - host disease ( gvhd ) prophylaxis included tacrolimus and short - term methotrexate .
twelve months after allo - bmt , the patient s serum / level was maintained at normal levels .
he remained in a state of remission , with only the complication of mild skin gvhd .
there are no established therapeutic regimens for pcl . several regimens that include an alkylating agent are sufficient to improve the overall survival ( os ) of pcl patients .
jimnez - zepeda and domnguez reported a median os of 6.8 months for pcl patients treated with a common chemotherapy regimen consisting of vincristine , adriamycin , and dexamethasone , versus 2 months for those who received melphalan and prednisolone.5 it has also been reported that a combination of intermediate doses of melphalan and dexamethasone obtained the highest level of response in pcl patients .
however , the median os was only 60 days for the cohort that achieved a partial or complete response.6 by comparison , bortezomib regimens show promise as induction regimens for pcl .
katodritou et al reported that a combination of bortezomib and dexamethasone prolonged os ( median , 12 months).7 the efficacy of pad has been reported by chan et al.8 similar to the case presented by chan et al , our case , inducted with pad , showed a very impressive clinical course .
as soon as pad was started , leukemic plasma cell levels rapidly decreased ( figure 1 ) .
in addition , anemia and platelet depletion improved , and acute heart and kidney dysfunction rapidly recovered .
after three pad cycles , serum / levels were normalized , without any adverse effects ( figure 2 ) . in the present case , the absolute values of the immunoglobulin / free light chains in the serum before and after therapy had to be very important
although pad is effective for pcl , it remains to be determined whether long - term survival is improved , because of a lack of long - term follow - up .
immunomodulatory drugs ( imids ) , such as thalidomide and lenalidomide , are as promising as bortezomib.9 , the reasons we did not choose imids were that lenalidomide was not approved in japan at the onset of the patient s pcl , and we decided to leave an opportunity to use thalidomide at his relapse .
our case represented a potential curative strategy for pcl , with the safe introduction of allo - immunization with a n onmyeloablative regimen following pad and hdt + asct . for multiple mm , the most common malignant disease in plasma cells ,
asct is regarded as the standard therapy for newly diagnosed cases in patients younger than 65 years .
however , few patients who undergo the procedure are free of disease for more than 10 years . on the other hand ,
allo - sct is a promising therapy . because of the graft - versus - myeloma effect ,
a lower relapse rate and longer remissions have been reported in patients receiving allo - sct.11 presumably , pcl may be the same as mm .
however , the high risk of transplant - related mortality ( 30%60% ) is a limitation of the use of allo - sct for mm . to overcome this limitation , maloney et al reported that combining a cytoreductive autograft with a nonmyeloablative allograft lowered transplant - related mortality by approximately 15%.12 meanwhile , ramasamy et al reported that alemtuzumab - based reduced intensity conditioning allogeneic transplantation.13 although progression - free survival of their patient cohort was comparable to previously published data of reduced intensity conditioning allogeneic transplantation in myeloma , there is no plateau on the survival curves , with a significant transplant - related mortality of 21% .
although nonmyeloablative conditioning reduces transplant - related mortality , it is difficult for patients older than 65 years to use our strategy . for them
we have a successful case of newly diagnosed primary pcl , treated with a regimen that included bortezomib and asct , followed by nonmyeloablative allo - sct .
this strategy is promising for pcl , which , though an extremely resistant disease , may become curable .
 plasma cell leukemia ( pcl ) is a rare disease that represents approximately 4% of plasma cell malignant disorders . 
 pcl consists of two variants : primary pcl presents in patients with no previous history of multiple myeloma , while secondary pcl consists of a leukemic transformation in a previously recognized multiple myeloma . 
 primary pcl is an extremely resistant , rapidly progressive , fatal disease , with a median overall survival of 6.8 months . 
 there is no standard therapeutic strategy , because no treatment option has been prospectively evaluated . 
 we describe a successful case of newly diagnosed primary pcl , treated with a regimen that included bortezomib , followed by auto stem cell transplantation and nonmyeloablative allogeneic stem cell transplantation . our patient has maintained remission status for over 12 months since undergoing the allogeneic stem cell transplantation . 
 this strategy is promising for pcl , which , though an extremely resistant disease , may become curable . 
Introduction
Case report
Discussion