scholarly journals In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain [published erratum appears in Blood 1995 Jun 1;85(11):3365]

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 436-447 ◽  
Author(s):  
PL Bergsagel ◽  
AM Smith ◽  
A Szczepek ◽  
MJ Mant ◽  
AR Belch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
Light Chain ◽  
Late Stage ◽  
Plasma Cells ◽  
Surface Expression ◽  
Lambda Light Chain ◽  
Cdr3 Region ◽  
Polymerase Chain ◽  
Ig Heavy Chain

Abstract Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the bone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical treatment on late stage CD19+ B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD19+ cells as do normal donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates that the CD19+ population includes cells sharing the same clonotypic CDR3 region as is detected in the BM plasma cells, for patients analyzed during chemotherapy or in relapse. They are also monotypic as defined by their cytoplasmic or surface expression of Ig kappa or lambda light chain. The light chain restriction is the same as that of the BM plasma cells. Individual patients observed over 1- to 2-year periods exhibit considerable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal Ig. The monoclonal blood CD19+ cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during transient remissions. Patients in the progressive phase of disease or in relapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the quantity of blood B cells approaches normal, phenotypically their quality is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38hi blood B cells had a cyclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse.

scholarly journals In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain [published erratum appears in Blood 1995 Jun 1;85(11):3365]

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 436-447 ◽  
Author(s):  
PL Bergsagel ◽  
AM Smith ◽  
A Szczepek ◽  
MJ Mant ◽  
AR Belch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
Light Chain ◽  
Late Stage ◽  
Plasma Cells ◽  
Surface Expression ◽  
Lambda Light Chain ◽  
Cdr3 Region ◽  
Polymerase Chain ◽  
Ig Heavy Chain

Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the bone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical treatment on late stage CD19+ B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD19+ cells as do normal donors. Analysis of the Ig heavy chain (IgH) gene rearrangements using polymerase chain reaction indicates that the CD19+ population includes cells sharing the same clonotypic CDR3 region as is detected in the BM plasma cells, for patients analyzed during chemotherapy or in relapse. They are also monotypic as defined by their cytoplasmic or surface expression of Ig kappa or lambda light chain. The light chain restriction is the same as that of the BM plasma cells. Individual patients observed over 1- to 2-year periods exhibit considerable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal Ig. The monoclonal blood CD19+ cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during transient remissions. Patients in the progressive phase of disease or in relapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the quantity of blood B cells approaches normal, phenotypically their quality is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characteristic of late-stage B or pre-plasma cells. CD38hi blood B cells had a cyclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse.

scholarly journals Metastatic Multiple Myeloma to the Skin

2019 ◽  
Vol 2019 ◽  
pp. 1-3
Author(s):  
Alex C. Holliday ◽  
Mohammed I. Khan ◽  
Sean E. Mazloom ◽  
Rahul N. Chavan ◽  
Douglas J. Grider
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Standard Treatment ◽  
Plasma Cells ◽  
Treatment Approach ◽  
Prognostic Indicator ◽  
Lambda Light Chain ◽  
Stage Disease ◽  
Poor Prognostic Indicator

Cutaneous involvement of multiple myeloma (MM) is uncommon, typically occurs in late stage disease, and is a poor prognostic indicator with an approximate eight month median survival. We present a 51-year-old man with relapsed lambda light chain MM who developed abrupt asymptomatic skin metastases. Biopsy revealed a dermis replete of atypical plasma cells, positive for CD138 and CD45. In situ hybridization confirmed lambda light chain restriction. Despite rescue antimyeloma therapy with the anti-CD38 drug daratumumab, he rapidly declined clinically and succumbed to the disease four weeks after presentation. A standard treatment approach for cutaneous MM does not currently exist; however, various techniques to detect cytogenetic abnormalities are emerging and will provide additional prognostic value and direct individualized therapy.

Marked efficacy of rituximab in two patients with Waldenstrom macroglobulinemia-like multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18548-e18548
Author(s):  
Christoph J. Heuck ◽  
Saad Zafar Usmani ◽  
Erming Tian ◽  
Qing Zhang ◽  
Frits Van Rhee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Plasma Cells ◽  
Single Agent ◽  
Organ Damage ◽  
Detailed Examination ◽  
Lambda Light Chain ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
First Case

e18548 Background: Rituximab (R) has been deemed to be ineffective in multiple myeloma (MM), despite CD20 expression in 10-15% of MM. Here we report two cases, selected by a genomic approach, with an excellent response to single agent R. Methods: as below Results: Patient 1: A 49 yr old male with IgG lambda MM with 80% bone marrow (BM) plasma cells (PC) and IgG level of 23 g/L had been treated elsewhere with one cycle of CRD. Here, we noted CD-2 subclass by gene expression profilin (GEP), however without spiked expression of CCND1 and CCND3 genes as manifestation of a t[11:14] or a t[6:14]. GEP further revealed a del 6q and overexpression of EBI2, both commonly seen in Waldenstrom Macroglobulinemia (WM). All findings were confirmed by FISH. Unsupervised clustering in the context of MGUS, untreated MM and WM-PC, confirmed WM-like MM in this patient. Sole therapy with R (750 mg/m2/d x 5d, weekly x 4, bi-weekly x 4 and then monthly) resulted in a reduction of IgG from 1850 mg/dL to 950 mg/dl and BM PC from 60% to 10% at 9 months and a decrease in sLFLC from 68 mg/dL to 10 mg/dL at 12 months follow up. Patient 2: Based on the above observation, we identified a second patient. This 37-yr old male had been diagnosed with lambda light chain MM 42 months earlier with a BM PC of 15%, lambda light-chain proteinuria of 1.9 g/d and sLFLC in the 200mg/dL range. Because of absence of CRAB criteria, he was followed expectantly. Rising BM PC to 50% and concern for end-organ damage motivated a detailed examination of GEP data. GEP showed high expression of CD20 and EBI2 and absence of CCND1 and CCND3 spikes. This was confirmed by FISH, which also revealed a del 6q. As in the first case, this patient co-segregated with WM. R treatment on the same schedule resulted in a reduction of sLFLC levels from 249 mg/dL to 29.9 mg/dl and of Bence Jones proteinuria from 1766 mg/d to 242 mg/d. Conclusions: The presumed lack of activity of R in MM needs to be revisited in light of the marked response noted in these 2 patients. Studies are in progress (a) to extend R therapy to similar cases, and (b) to more fully characterize the prevalence of genetic/phenotypic characteristics, as seen in these 2 cases, among several thousand MM patients. This updated information will be presented at the meeting.

A High Frequency of Circulating B Cells Share Clonotypic Ig Heavy-Chain VDJ Rearrangements With Autologous Bone Marrow Plasma Cells in Multiple Myeloma, as Measured by Single-Cell and In Situ Reverse Transcriptase-Polymerase Chain Reaction

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2844-2855 ◽  
Author(s):  
Agnieszka J. Szczepek ◽  
Karen Seeberger ◽  
Juanita Wizniak ◽  
Michael J. Mant ◽  
Andrew R. Belch ◽  
...  
Keyword(s):  
B Cells ◽  
Single Cell ◽  
Heavy Chain ◽  
Plasma Cells ◽  
Patient Specific ◽  
Rt Pcr ◽  
Specific Primers ◽  
Polymerase Chain ◽  
Ig Heavy Chain

In multiple myeloma (MM), the VDJ rearrangement of the immunoglobulin heavy chain expressed by MM plasma cells provides a unique clonotypic marker. Although clonotypic MM cells have been found in the circulation, their number has been controversial. Our objective was to provide direct evidence, using single-cell assays, for the frequency of clonotypic cells in blood of 18 MM patients, and to confirm their identity as B cells. The clonotypic Ig heavy-chain (IgH) VDJ was determined from single plasma cells using consensus reverse transcriptase-polymerase chain reaction (RT-PCR), subcloning, and sequencing. For all patients, using patient-specific primers, clonotypic transcripts were amplified from 10 or more individual plasma cells. Using in situ RT-PCR, for all patients greater than 80% of plasma cells were found to be clonotypic. Three separate methods, RT-PCR, single-cell RT-PCR, and in situ RT-PCR, were used to analyze clonotypic cells in peripheral blood mononuclear cells (PBMC) from MM patients. Sequencing of the IgH transcripts expressed by individual cells obtained by limiting dilution of freshly isolated PBMC from a MM patient showed that all B cells expressed an identical CDR3. This intraclonal homogeneity indicates an escape from antigenic-selection, characteristic of malignant B cells. For this patient, the frequency of clonotypic PBMC, about 25%, was comparable to the number of PBMC B cells (34%). Because the PBMC included less than 1% plasma cells, virtually all clonotypic PBMC must be B cells. Using single-cell RT-PCR, clonotypic IgH transcripts were identified in individual sorted B cells from blood. To accurately quantify the number of clonotypic B cells, sorted B cells derived from 18 MM patients (36 samples) and 18 healthy donors (53 samples) were analyzed using in situ RT-PCR with patient-specific primers. Clonotypic transcripts were not detectable among normal B cells. For the 18 MM patients, a mean of 66% ± 4% (SE) of blood B cells were clonotypic (range, 9% to 95%), with mean absolute number of 0.15 ± .02 × 109/L blood. Over time in individual patients, conventional chemotherapy transiently decreased circulating clonotypic B cells. Their numbers were increased in granulocyte colony-stimulating factor (G-CSF)– mobilized blood of one patient. However, clonotypic B cells of a one patient became undetectable after allogeneic transplant, correlating with complete remission. Although contributions to MM spread and progression is likely, their malignant status and impact has yet to be clarified. Their high frequency in the blood, and their resistence to conventional chemotherapy suggests that the number of circulating clonotypic cells should be clinically monitored, and that therapeutic targeting of these B cells may benefit myeloma patients. © 1998 by The American Society of Hematology.

scholarly journals Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2326-2335 ◽  
Author(s):  
MH Bakkus ◽  
C Heirman ◽  
I Van Riet ◽  
B Van Camp ◽  
K Thielemans
Keyword(s):  
Multiple Myeloma ◽  
Somatic Mutations ◽  
Plasma Cells ◽  
Somatic Hypermutation ◽  
Specific Primers ◽  
Clonal Proliferation ◽  
A Cell ◽  
Polymerase Chain ◽  
Vh Genes ◽  
Ig Heavy Chain

Abstract To investigate whether somatic hypermutation occurs in multiple myeloma (MM) Ig VH region genes, we have cloned and sequenced the expressed VH genes from five cases of MM. The sequences were obtained after polymerase chain reaction (PCR) on total RNA isolated from the bone marrow, using 5′ VH family-specific leader and 3′ C gamma- or C alpha- specific primers. MM-specific CDR3 oligonucleotides were produced to isolate VH genes expressed by the malignant plasma cells. In all five cases, the productive Ig gene used the VH3 family. Extensive sequence analysis of multiple independent M13 clones showed no intraclonal variation with no evidence for ongoing somatic hypermutation in MM VH region genes. We were able to identify possible germline counterparts of the expressed VH genes in two cases. Comparison of these genes shows that the MM VH region genes have somatic mutations characteristic for an antigen-driven process. In the other three cases, no close homology could be found with published VH3 sequences. These findings implicate that, in MM, clonal proliferation takes place in a cell type that has already passed through the phase of somatic hypermutation.

A High Frequency of Circulating B Cells Share Clonotypic Ig Heavy-Chain VDJ Rearrangements With Autologous Bone Marrow Plasma Cells in Multiple Myeloma, as Measured by Single-Cell and In Situ Reverse Transcriptase-Polymerase Chain Reaction

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2844-2855 ◽  
Author(s):  
Agnieszka J. Szczepek ◽  
Karen Seeberger ◽  
Juanita Wizniak ◽  
Michael J. Mant ◽  
Andrew R. Belch ◽  
...  
Keyword(s):  
B Cells ◽  
Single Cell ◽  
Heavy Chain ◽  
Plasma Cells ◽  
Patient Specific ◽  
Rt Pcr ◽  
Specific Primers ◽  
Polymerase Chain ◽  
Ig Heavy Chain

Abstract In multiple myeloma (MM), the VDJ rearrangement of the immunoglobulin heavy chain expressed by MM plasma cells provides a unique clonotypic marker. Although clonotypic MM cells have been found in the circulation, their number has been controversial. Our objective was to provide direct evidence, using single-cell assays, for the frequency of clonotypic cells in blood of 18 MM patients, and to confirm their identity as B cells. The clonotypic Ig heavy-chain (IgH) VDJ was determined from single plasma cells using consensus reverse transcriptase-polymerase chain reaction (RT-PCR), subcloning, and sequencing. For all patients, using patient-specific primers, clonotypic transcripts were amplified from 10 or more individual plasma cells. Using in situ RT-PCR, for all patients greater than 80% of plasma cells were found to be clonotypic. Three separate methods, RT-PCR, single-cell RT-PCR, and in situ RT-PCR, were used to analyze clonotypic cells in peripheral blood mononuclear cells (PBMC) from MM patients. Sequencing of the IgH transcripts expressed by individual cells obtained by limiting dilution of freshly isolated PBMC from a MM patient showed that all B cells expressed an identical CDR3. This intraclonal homogeneity indicates an escape from antigenic-selection, characteristic of malignant B cells. For this patient, the frequency of clonotypic PBMC, about 25%, was comparable to the number of PBMC B cells (34%). Because the PBMC included less than 1% plasma cells, virtually all clonotypic PBMC must be B cells. Using single-cell RT-PCR, clonotypic IgH transcripts were identified in individual sorted B cells from blood. To accurately quantify the number of clonotypic B cells, sorted B cells derived from 18 MM patients (36 samples) and 18 healthy donors (53 samples) were analyzed using in situ RT-PCR with patient-specific primers. Clonotypic transcripts were not detectable among normal B cells. For the 18 MM patients, a mean of 66% ± 4% (SE) of blood B cells were clonotypic (range, 9% to 95%), with mean absolute number of 0.15 ± .02 × 109/L blood. Over time in individual patients, conventional chemotherapy transiently decreased circulating clonotypic B cells. Their numbers were increased in granulocyte colony-stimulating factor (G-CSF)– mobilized blood of one patient. However, clonotypic B cells of a one patient became undetectable after allogeneic transplant, correlating with complete remission. Although contributions to MM spread and progression is likely, their malignant status and impact has yet to be clarified. Their high frequency in the blood, and their resistence to conventional chemotherapy suggests that the number of circulating clonotypic cells should be clinically monitored, and that therapeutic targeting of these B cells may benefit myeloma patients. © 1998 by The American Society of Hematology.

Schwannoma with monoclonal plasma cell infiltration

2009 ◽  
Vol 111 (3) ◽  
pp. 509-511 ◽  
Author(s):  
Joshua Plaut ◽  
Malcolm Galloway ◽  
Anna Childerhouse ◽  
Robert Bradford
Keyword(s):  
Cell Population ◽  
Plasma Cell ◽  
Vestibular Schwannoma ◽  
Light Chain ◽  
Histological Analysis ◽  
Plasma Cells ◽  
Systemic Disease ◽  
Lambda Light Chain ◽  
Plasma Cell Neoplasm ◽  
Polymerase Chain

The authors report a very rare case of a vestibular schwannoma with an infiltrate of monoclonal plasma cells. A 45-year-old woman underwent routine excision of a presumed vestibular schwannoma. Histological analysis revealed the presence of a distinct lambda light chain restricted plasma cell population within the schwannoma. The light chain restriction and polymerase chain reaction–demonstrated monoclonality of the plasma cell population suggested the co-occurrence of a plasma cell neoplasm within a schwannoma. A search for systemic disease of plasma cell origin was unremarkable. A search of the literature suggests that this is the first report of such an occurrence.

scholarly journals A Novel Case of Direct Antiglobulin Test-Negative Intravascular Hemolysis in a Patient with Smoldering Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4539-4539
Author(s):  
Selina Dobing ◽  
Nikolas Desilet ◽  
Irwindeep Sandhu ◽  
Lauren Bolster
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Case Reports ◽  
Alternative Pathway ◽  
Plasma Cell Dyscrasia ◽  
Intravascular Hemolysis ◽  
Lambda Light Chain

Abstract Objectives: 1. Describe a case of severe DAT-negative intravascular hemolysis in plasma cell dyscrasia. 2. Discuss a potential novel mechanism of light-chain mediated hemolysis. A 34-year old woman was admitted to hospital with fatigue and severe iron deficiency anemia (hemoglobin 47 g/dL, MCV 59 fL, ferritin 2 mcg/L). Her medical history included a presumptive diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) from five years prior. She was transfused 2 units of red cells, started on oral iron and folate, and was discharged symptom-free with a hemoglobin of 71 g/dL. She returned three days later with abdominal pain, dark urine, and evidence of intravascular hemolysis. She was admitted for empiric treatment of PNH with high-dose glucocorticoids and therapeutic enoxaparin for presumed intra-abdominal thrombosis. Her flow cytometry, including granulocytes, was negative for PNH. Her direct antiglobulin test (DAT) was negative for IgG antibodies but positive for C3 complement. A thorough hemolysis workup was negative, including schistocytes and Donath Landsteiner testing. ADAMTS13 testing was uninterpretable due to high plasma free hemoglobin. Despite corticosteroids, brisk hemolysis continued with 10 units of RBCs required over 5 days to maintain a stable hemoglobin. Plasma free hemoglobin reached 1147 mg/L, prompting therapeutic plasmapheresis for renal protection by the end of day 5. She deteriorated clinically after her first plasmapheresis with acute confusion (GCS 10) and lactic acidosis. She was empirically treated for seizure with levetiracetam. CT and MRI scans of her brain and lumbar puncture were normal. Her consciousness improved with daily plasmapheresis. A bone marrow biopsy performed on day twelve of glucocorticoid therapy found monoclonal plasma cell proliferation of 15% with marked lambda light chain predominance (20:1) (Figure 1). Repeat bone marrow biopsy 3 months post-steroid therapy still revealed 10% clonal plasma cells. Hemolysis can be a rare presentation of plasma cell dyscrasia. Case reports of both autoimmune hemolytic anemia and microangiopathic hemolytic anemia associated with multiple myeloma exist. In our case, there was no evidence of a microangiopathic process, making thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic-uremic syndrome (aHUS) unlikely. DAT was negative for IgG but did demonstrate C3 complement molecules bound to red cells. No previous case reports of complement-mediated hemolysis and multiple myeloma were found on literature review. We report the first in vivo association between complement-mediated hemolysis and plasma cell dyscrasia. Complement pathways bridge the innate and acquired immune systems by helping select cells to be targeted by the acquired immune system. The alternative complement pathway does not require an antigen-antibody interaction to become active; rather, it is controlled by direct binding of complement and regulated by cofactor molecules. Jokiranta et al. (J Immunol 1999) identified a monoclonal Ig-lambda dimer that efficiently activated the alternative pathway of complement, triggering complement molecules to enhance hemolysis of serum in vitro. This "miniautoantibody" specifically bound and blocked the function of complement factor H, inhibiting enzymatic inactivation of fluid-phase C3b with uncontrolled activation of the alternative pathway. It is possible that the relative immune dysfunction in this patient's plasma cell dyscrasia led to a disturbance in the alternate complement pathway, perhaps due to dimerization of abnormal lambda light chains, resulting in complement-mediated intravascular hemolysis. Glucocorticoids and plasmapheresis may have helped manage hemolysis in this case. By diagnostic criteria, this patient has smoldering myeloma, with urine monoclonal protein (1.2 g/24 hours), clonal bone marrow plasma cells (10-15%), and absence of myeloma-defining events. We have elected to manage her as such, with close observation. Further work-up performed for her plasma cell dyscrasia included a normal MRI of spine and pelvis. Over a year later, there has been no recurrence of hemolysis. Consideration will be given to treatment if she progresses to overt multiple myeloma. Figure 1. A. Aspirate showing abnormal plasma cells. B. Trephine CD138 stain. C. Trephine kappa light chain stain. D. Trephine lambda light chain stain. Figure 1. A. Aspirate showing abnormal plasma cells. B. Trephine CD138 stain. C. Trephine kappa light chain stain. D. Trephine lambda light chain stain. Disclosures Sandhu: Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

scholarly journals Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2326-2335 ◽  
Author(s):  
MH Bakkus ◽  
C Heirman ◽  
I Van Riet ◽  
B Van Camp ◽  
K Thielemans
Keyword(s):  
Multiple Myeloma ◽  
Somatic Mutations ◽  
Plasma Cells ◽  
Somatic Hypermutation ◽  
Specific Primers ◽  
Clonal Proliferation ◽  
A Cell ◽  
Polymerase Chain ◽  
Vh Genes ◽  
Ig Heavy Chain

To investigate whether somatic hypermutation occurs in multiple myeloma (MM) Ig VH region genes, we have cloned and sequenced the expressed VH genes from five cases of MM. The sequences were obtained after polymerase chain reaction (PCR) on total RNA isolated from the bone marrow, using 5′ VH family-specific leader and 3′ C gamma- or C alpha- specific primers. MM-specific CDR3 oligonucleotides were produced to isolate VH genes expressed by the malignant plasma cells. In all five cases, the productive Ig gene used the VH3 family. Extensive sequence analysis of multiple independent M13 clones showed no intraclonal variation with no evidence for ongoing somatic hypermutation in MM VH region genes. We were able to identify possible germline counterparts of the expressed VH genes in two cases. Comparison of these genes shows that the MM VH region genes have somatic mutations characteristic for an antigen-driven process. In the other three cases, no close homology could be found with published VH3 sequences. These findings implicate that, in MM, clonal proliferation takes place in a cell type that has already passed through the phase of somatic hypermutation.

Multiple Myeloma Is Exceptional in Paediatrics: Report of One Case From 1200 Patients in a Single Institution.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4957-4957
Author(s):  
Sophie Auger ◽  
Genevieve Margueritte ◽  
Renaud Tichit ◽  
Basheer Khalil ◽  
Philippe Quittet ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Light Chain ◽  
Plasma Cells ◽  
Complete Response ◽  
Cell Labelling ◽  
Bone Lesions ◽  
Lambda Light Chain ◽  
Allogenic Stem Cell Transplantation ◽  
Monoclonal Component

Abstract Abstract 4957 Multiple myeloma (MM), a disease usually observed in elderly patients, is extremely rare below 30 years of age. We present a case of a MM in a 10-year-old boy who has been admitted in September 2007 to the paediatric unit from the university hospital in Montpellier, with a fracture of his left femoral bone after a rugby match. In his history, he was known to present a juvenile myelomonocytic leukaemia (JMML) when he was 4-month-old in December 1998. For this diagnosis, he has been treated with aracytine and hydroxyurea for 4 years and he got a complete response (CR) since July 2005. At admission, surprisingly the radiography showed two lytic bone lesions. At MRI, it was found proximal and distal medullar metadiaphyseal spreading associated to a fracture, with no clinical symptom. The histology of the two tissue biopsies showed large dystrophic plasma cells, MI 15 positive with no clear evidence of a monoclonality by using light chain immunostaining. The bone marrow biopsy showed an interstitial infiltrate of dystrophic plasma cells, with only lambda light chain expression. Five percent of dystrophic plasma cells were observed on bone marrow smears. The monoclonal component IgG Lamda was 3.56 G/dL. Free kappa and lambda light chain dosages were respectively 5.65 mg/L and 766 mg/L, with a kappa lambda ratio under 0.01. Proteinuria was 0.64 g/day, haemoglobin was 106 G/L, and Beta2 microglobulin was 2.6mg/L. There was no hypercalcaemia and serum albumin and creatinin clearance were normal. Plasma cell labelling index (PCLI) was 1.16 % in the bone marrow and 6.6 circulating plasma cells/μL were counted in peripheral blood. Unfortunately, gene expression profiling analysis failed due to the low number of cells. PET scan found multiple uptakes in femoral, vertebral costal and sternal bones. So, this boy presented a multiple myeloma with stage IIIA according to Durie Salmon staging and ISS (International staging system) I. He underwent nine cycles of bortezomib (1.3 mg/m2 D1, D4, D8, D11) and dexamethazone (40mg/D, D1 to D4) to reach a complete response. A myeloablative allogenic stem cell transplantation was performed from his sister the 11th of September 2008, with a regimen based on cyclophosphamide (60mg/Kg, D1, D2) and TBI 12Gy. The immunosuppressive regimen associated methotrexate (D1, D3, D6) and cyclosporine. The graft contained 4.14 ×108 MNC/kg, 4.19 106 CD34/Kg and 6.16 107 CD3/Kg. At Day 120, a full donor chimerism was obtained, with no GVHd, but the monoclonal component reappeared. He received only a single cycle of bortezomib and dexamethazone because of severe peripheral neuropathy and gastro-intestinal intolerance. A second CR has been obtained in June 2009. Minimal residual disease by flow cytometry will be soon performed in order to discuss donor lymphocyte infusions. We report a case of MM during the childhood that is extremely rare. Very few cases have been reported in the literature. In this particular case, the patient has been also treated for a JMML that may have a relationship with the MM. Unfortunately, no cytogenetic or DNA profiling has been performed. To our knowledge, it is the first time that such feature is reported. The overall survival (OS) reported by the Mayo clinic in a series of 10 children was 87 months that may suggests a better OS as compared to adults (Blade J, Kyle RA, Greipp PR. Multiple myeloma in patients younger than 30 years - Report of 10 cases and review of the literature. Arch Intern Med. 1996;156:1463-8). Disclosures No relevant conflicts of interest to declare.

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