Chronic neutrophilic leukemia and multiple myeloma: An association with λ light chain expression

Cancer ◽  
1990 ◽  
Vol 66 (1) ◽  
pp. 162-166 ◽  
Author(s):  
Graham R. Standen ◽  
Bharat Jasani ◽  
Michael Wagstaff ◽  
Charles A. J. Wardrop
2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8512-8512 ◽  
Author(s):  
Noemí Puíg ◽  
Teresa Contreras ◽  
Bruno Paiva ◽  
M Teresa Cedena ◽  
Joaquin Martinez-Lopez ◽  
...  

8512 Background: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients (pts) in which the primary endpoint is the achievement of sustained minimal residual disease (MRD) negativity in the bone marrow (BM) by next generation flow (NGF). The value of BM MRD assessment in MM is proven, but alternative, non-invasive methods, accurately reflecting disease burden are needed. Methods: Pts received six 4-week cycles of KRd as induction (K:36mg/m2 twice weekly, R: lenalidomide 25mg po od days 1-21 and d:dexamethasone 40mg po weekly) followed by melphalan 200mg/m2, two further cycles of KRd as consolidation and up to 2 years of Rd (R:10mg/d, d:20mg/week). Efficacy was analyzed in parallel in BM samples by NGF and in serum by SPEP/IFE and QIP-MS/QIP-FLC-MS in 52 out of the 90 pts enrolled in the trial. Standard and MRD responses were carried out as per the IMWG guidelines. For QIP-MS serum immunoglobulins were purified using polyclonal antibodies (anti-IgG, -IgA, -IgM, -total κ and -total λ light chain, -free κ and -free λ light chain). Mass spectra were generated on a MALDI-TOF-MS system. Results: Overall response rate (ORR) was 98% post-induction, 98% post-ASCT, and 100% post-consolidation; 38.4%, 61.5% and 68.6% of pts reached ≥ complete response at each time-point and, among them, 23%, 44% and 55% achieved flow MRD-negativity. Using the combination of QIP-MS/QIP-FLC-MS, the percentage of pts without detectable disease at each timepoint lowered to 12%, 27% and 38% reflecting the higher sensitivity of the method. Against NGF, QIP-MS/QIP-FLC-MS provided negative predictive values of 67%, 92% and 89% (p = 0,0206; p < 0,001; p = 0,003) and identified disease in 95%, 97% and 92% of pts that were positive by NGF-MRD at each respective timepoint. Three pts from this cohort have progressed so far: two were NGF+/MS+ at the three timepoints whilst 1 remained NGF- but QIP-MS/FLC-MS+ throughout. Conclusions: The GEM-CESAR treatment strategy induces a high ORR in HRsMM pts, and the % of cases achieving flow-MRD negativity post-ASCT meets the primary endpoint of the trial. The combined use of QIP-MS and FLC-MS offers higher sensitivity relative to standard methods and may provide relevant information about the right timing for performing a BM aspirate/biopsy. Clinical trial information: NCT02415413 .


PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33372 ◽  
Author(s):  
Paolo Arosio ◽  
Marta Owczarz ◽  
Thomas Müller-Späth ◽  
Paola Rognoni ◽  
Marten Beeg ◽  
...  

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S31-S32
Author(s):  
J K Lee ◽  
A Flowers ◽  
J Williams ◽  
S Li ◽  
X Yi ◽  
...  

Abstract Introduction/Objective In rare cases, the conventional immunofixation gel electrophoresis technique fails to detect the light chain of an M-protein. We report a case of immunoglobulin (Ig) D multiple myeloma with a hidden lambda (λ) light chain. Methods/Case Report Capillary electrophoresis (CE) (Sebia CAPILLARYS 2) was used to detect and quantify M- proteins in serum specimens. Immunosubtraction (IS) on the CAPILLARYS 2 systems was used to identify the classes of M-proteins. Conventional gel immunofixation electrophoresis (IFE) was performed, using monospecific antisera for IgD, IgE, kappa (κ) or λ in the Sebia HYDRASYS system, and IgG, IgA, IgM, κ or λ in the Helena SPIFE3000 system. Beta-mercaptoethanol (BME) with Fluidil were used as reduction agents. Results (if a Case Study enter NA) Results of serum CE showed two abnormal peaks in beta 2 and gamma regions, suspected to be positive for M-proteins. IS results showed subtraction for λ light chain only in both peaks, suggesting two monoclonal λ light chains. In contrary, no monoclonal λ light chain was detected in gamma region by IFE (Sebia). Epitope masking in the folded monoclonal protein was suspected to cause the “hidden λ light chain” and was further investigated by two laboratory approaches. IFE performed on the Helena SPIFE3000 system found two λ bands in beta 2 and gamma regions, which was consistent with the results from IS. The treatment of BME with Fluidil helped unmasking the hidden epitope and revealed the λ band in gamma region on IFE (Sebia). Conclusion The medical laboratories should be aware of the described scenario. The failure to detect light chains of certain intact M-proteins is most likely due to the structurally inaccessibility of light chains. It is recommended that treatment with reduction agents or use of an alternative methodology or IS might be helpful for investigating suspected heavy chain only cases, due to the limitation of conventional methodology.


2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Evelyn Taiwo ◽  
Huiying Wang ◽  
Robert Lewis

A 63-year-old female was incidentally found to have leukocytosis and referred to the hematology service for evaluation. Complete blood count (CBC) revealed neutrophilia with band predominance and mild thrombocytopenia. Peripheral blood flow cytometry was unremarkable without any evidence of lymphoproliferative disorder or myeloblasts. Bone marrow aspiration and biopsy revealed a markedly hypercellular marrow with myeloid lineage predominance and approximately 10% plasma cells. The monoclonal gammopathy was determined as lambda light chain with a kappa/lambda ratio of 0.06. Cytogenetics revealed normal karyotype, JAK2 kinase was negative, and rearrangement of BCR-ABL1, PDGFRA, PDGFRB, and FGFR1 was negative. The patient was diagnosed with chronic neutrophilic leukemia (CNL) associated with light chain multiple myeloma, complicated by a subdural hemorrhage. She was treated with hydroxyurea and bortezomib/dexamethasone and had complete response with normalization of CBC and kappa/lambda ratio. To the best of our knowledge, we report the first case of chronic neutrophilic leukemia and multiple myeloma treated with bortezomib/dexamethasone.


2002 ◽  
Vol 48 (10) ◽  
pp. 1805-1811 ◽  
Author(s):  
Roshini S Abraham ◽  
M Cristine Charlesworth ◽  
Barbara AL Owen ◽  
Linda M Benson ◽  
Jerry A Katzmann ◽  
...  

Abstract Background: Patients with multiple myeloma often have Bence Jones proteins composed of free monoclonal light chains of the κ or λ type in their urine. Usually, these light chains exist as monomeric or dimeric forms, but rarely, larger molecules, such as tetramers, have been reported in the serum. Methods and Results: We report the presence of trimeric complexes of λ light chain dimers in a patient who was diagnosed with a free λ light chain multiple myeloma 2 years earlier and subsequently underwent a stem cell transplant. Recently, the patient presented with a large serum M-spike (23 g/L) by protein electrophoresis. The spike consisted of monoclonal λ light chains without a heavy chain. The urine contained only 8 mg of λ light chain in a 24-h specimen. Quantitative analysis of the serum and urinary free light chains (FLCs) indicated the probability of larger aggregates of FLCs. Size-exclusion chromatography, electrophoresis, analytical ultracentrifugation, and mass spectrometric studies of the serum revealed almost exclusively the presence of trimolecular aggregates of λ light chain dimers without other multimeric species. Conclusion: Monoclonal λ light chains may present as hexameric aggregates that cannot be cleared by renal excretion.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5184-5184
Author(s):  
Juan Li ◽  
Shao-Kai Luo ◽  
Ying Zhao

Abstract Multiple myeloma is still an incurable malignancy with low complete remission rate and a high recurrence rate by conventional therapy. The fludarabine-based regimen of eliminating the B lymphocytes may reduce or suppress the relapse of multiple myeloma. We treated the patients with relapsed and refractory multiple myeloma with FMD (fludarabine 35 mg/m2/d, d1~3, mitoxantrone 8 mg/m2/d, d1 and dexamethasone 20mg/d, d1~4). The results are encouraging. Case one: A 47 year-old female presented with lumbosacral pain (for 2 months), dull pain in the low back, palpitations, distress, and shortness of breath. Her peripheral blood examination showed that her white blood cell (WBC) count was 5.71×109/L, the hemoglobin concentration was 81 g/L and the platelet count was 181×109/L. The serum IgG was 118.0g/L, λ light chain was 115.84 g/L, globulin was 133 g/L, albumin was 26 g/L, and β2-MG was 3491.8 μg/L. The serum Ca2+ was 2.2 mmol/L. The urine Bence-Jones protein electrophoresis was negative. The immunoelectrophoretic analysis showed a monoclonal protein: IgG-lambda. A bone marrow aspirate revealed 38% plasma cells. The body bone radiograph revealed generalized osteoporosis and depressed fracture of L2 and L4. She was diagnosed as Multiple Myeloma. The patient subsequently began 5 courses of VADM every 4 weeks (vincristine 0.5 mg on Days 1–4, THP 10 mg on Days 1–4, dexamethasone 20 mg on Days 1–4, Melphan 6 mg BID on Days 1–4). The lumbodynia was relieved after chemotherapy. But after 5 courses of VADM, her hemoglobin level was 81 g/L, IgG was 40.9 g/L, λ light chain was 33.28 g/L, albumin was 56 g/L, and β2-MG was 2156.2 μg/L. A BM study showed 30% plasma cells. The body bone radiograph was the same as before. Then she was treated with 3 courses of FMD. The symptoms of lumbodynia were relieved. A bone marrow study showed 14% plasma cells. The hemoglobin level was 125 g/L, IgG was 21.9 g/L, λ light chain was 31.3 g/L, albumin was 63 g/L, and β2-MG was 1670.6 μg/L. No more new lytic lesion appeared. There were no obvious side effects during the treatment. Case two: A 57-year-old male presented with shortness of breath, palpitations caused by hard work and pain of the lower back, which had been continuing for 4 months. Prior to his admission, the bone marrow showed a 19.5% plasma cells. The immunoelectrophoretic analysis disclosed the presence of a monoclonal component of IgA-kappa protein. Serum levels of immunoglobulin were 7.45 g/L for IgA and 15.04 g/L for kappa. Serum creatinine was 123 mmol/L, BUN 5.2 mmol/L, calcium 2.3 mmol/L, β2-microglobulin 6114.5 mg/L and hemoglobin was 61 g/L. The bone X-ray showed generalized osteoporosis and depressed fracture of L2 and L4. The patient was diagnosed as multiple myeloma and received 2 cycles of M2 and 2 cycles of VAD. But his symptoms did not improve and pain increased. After admission, the BM smear showed plasma cells of 46%. Serum IgA was 9.91 g/L, kappa was 17.79 g/L, calcium was 2.5 mmol/L, β2-microglobulin was 3338.8 mg/L, and hemoglobin was 84 g/L. The patient was given treatment with the regimen of FMD, repeated every 4 weeks. Four months later, after the 3 cycles of FMD were administered, the BM showed only 16% of plasma cells in smear specimen. Serum IgA was 8.25 g/L, kappa was 8.39 g/L, creatinine was 103 mmol/L, BUN was 7.0 mmol/L, calcium was 2.2 mmol/L, β2-microglobulin was 2926.0 mg/L, and hemoglobin was 112 g/L. The bone X-ray did not show new lytic lesions. So far 8 months after finishing 8 cycles of FMD, the patient was in a good condition and had no bone pain.


2016 ◽  
Vol 25 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Benoit Brilland ◽  
Johnny Sayegh ◽  
Anne Croue ◽  
Frank Bridoux ◽  
Jean-François Subra ◽  
...  

Light chain deposition disease (LCDD) is a rare multisystemic disorder associated with plasma cell proliferation. It mainly affects the kidney, but liver and heart involvement may occur, sometimes mimicking the picture of systemic amyloidosis. Liver disease in LCDD is usually asymptomatic and exceptionally manifests with severe cholestatic hepatitis. We report the case of a 66-year-old female with κ-LCDD and cast nephropathy in the setting of symptomatic multiple myeloma who, after a first cycle of bortezomib-dexamethasone chemotherapy, developed severe and rapidly worsening intrahepatic cholestasis secondary to liver κ-light chain deposition. Intrahepatic cholestasis was attributed to LCDD on the basis of the liver histology and exclusion of possible diagnoses. Chemotherapy was maintained and resulted in progressive resolution of cholestasis. We report here an uncommon presentation of LCDD, with prominent liver involvement that fully recovered with bortezomib-based chemotherapy, and briefly review the relevant literature. Abbreviations: AKI: Acute kidney injury; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CMV: Cytomegalovirus; EBV: Epstein–Barr virus; GGT: gamma-glutamyl transferase; HSV: Herpes simplex virus; LC: light chain; LCDD: Light chain deposition disease; MIDD: Monoclonal immunoglobulin deposition disease; MM: Multiple myeloma.


Author(s):  
Mathieu Dupré ◽  
Magalie Duchateau ◽  
Rebecca Sternke-Hoffmann ◽  
Amelie Boquoi ◽  
Christian Malosse ◽  
...  

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