scholarly journals Peripheral Neuropathy and VIth Nerve Palsy Related to Randall Disease Successfully Treated by High-Dose Melphalan, Autologous Blood Stem Cell Transplantation, and VIth Nerve Decompression Surgery

2010 ◽  
Vol 2010 ◽  
pp. 1-3
Author(s):  
C. Foguem ◽  
P. Manckoundia ◽  
P. Pfitzenmeyer ◽  
J.-L. Dupond
Keyword(s):  
Peripheral Neuropathy ◽  
Light Chain ◽  
Nerve Palsy ◽  
Motor Nerve ◽  
High Dose ◽  
Decompression Surgery ◽  
Kappa Light Chain ◽  
Light Chain Immunoglobulin ◽  
High Dose Melphalan ◽  
Nerve Decompression Surgery

Randall disease is an unusual cause of extraocular motor nerve (VI) palsy. A 35-year-old woman was hospitalized for sicca syndrome. The physical examination showed general weakness, weight loss, diplopia related to a left VIth nerve palsy, hypertrophy of the submandibular salivary glands, and peripheral neuropathy. The biological screening revealed renal insufficiency, serum monoclonal kappa light chain immunoglobulin, urinary monoclonal kappa light chain immunoglobulin, albuminuria, and Bence-Jones proteinuria. Bone marrow biopsy revealed medullar plasma cell infiltration. Immunofixation associated with electron microscopy analysis of the salivary glands showed deposits of kappa light chains. Randall disease was diagnosed. The patient received high-dose melphalan followed by autostem cell transplantation which led to rapid remission. Indeed, at the 2-month followup assessment, the submandibular salivary gland hypertrophy and renal insufficiency had disappeared, and the peripheral neuropathy, proteinuria, and serum monoclonal light chain had decreased significantly. The persistent diplopia was treated with nerve decompression surgery of the left extraocular motor nerve. Cranial nerve complications of Randall disease deserve to be recognized.

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

2010 ◽  
Vol 28 (33) ◽  
pp. 4976-4984 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Asher Chanan-Khan ◽  
Nelson Leung ◽  
Heinz Ludwig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Light Chain ◽  
Renal Injury ◽  
High Dose ◽  
Acute Renal Injury ◽  
High Dose Dexamethasone ◽  
Cast Nephropathy ◽  
High Dose Melphalan

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

scholarly journals Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer.

1989 ◽  
Vol 9 (10) ◽  
pp. 4239-4247 ◽  
Author(s):  
R A Currie ◽  
R G Roeder
Keyword(s):  
B Cell ◽  
Binding Site ◽  
Light Chain ◽  
Specific Binding ◽  
Specific Factor ◽  
Immunoglobulin Gene ◽  
Kappa Light Chain ◽  
Nf Kappa B ◽  
Light Chain Immunoglobulin ◽  
A Site

A 215-base-pair (bp) region of the mouse MOPC 41 kappa light-chain immunoglobulin gene enhancer has been analyzed for specific binding of lymphoid and nonlymphoid nuclear factors. Mobility shift assays with a series of overlapping DNA fragments have mapped DNA-binding sites for three unique factors. The B-cell-specific (OTF-2) and ubiquitous (OTF-1) octamer-binding transcription factors specifically bound to a site centered about 136 bp 5' of the nuclear factor NF-kappa B site. A third specific factor, NF-kappa E, bound to a site that was about 75 bp 5' of the NF-kappa B site and within a region important for enhancer function. This novel factor was found in both mature B and HeLa cell nuclei. B-cell OTF-2, B-cell OTF-1, and HeLa OTF-1 bound to the kappa enhancer and kappa promoter octamer sites with similar affinities despite a 2-bp difference in the kappa enhancer octamer sequence. However, DNase I footprint analyses indicated that affinity-purified OTF-2 bound both to the enhancer OTF site and, surprisingly, to 80 bp of A + T-rich flanking sequence. Moreover, methylation interference studies demonstrated distinct differences in OTF interactions between the consensus octamer in the kappa promoter and the nonconsensus octamer identified in the enhancer. This novel observation of an OTF-binding site in the kappa enhancer provides a common link with the OTF sites in the promoter-proximal regions of all kappa promoters and thus mirrors the structural arrangement of OTF sites found in the promoters and enhancers of immunoglobulin heavy-chain genes.

Treatment of Relapsed Myeloma in a Patient With Renal Insufficiency

2018 ◽  
Vol 36 (20) ◽  
pp. 2012-2016
Author(s):  
Joan Bladé ◽  
Laura Rosiñol ◽  
María Teresa Cibeira ◽  
Carlos Fernández de Larrea
Keyword(s):  
Serum Creatinine ◽  
Light Chain ◽  
Progressive Disease ◽  
M Protein ◽  
Bone Lesions ◽  
High Dose ◽  
Kappa Light Chain ◽  
Urine Protein ◽  
Urine Protein Excretion ◽  
Protein Excretion

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old man was diagnosed in March 2010 with stage III immunoglobulin G kappa multiple myeloma (MM) after presenting with bone pain as a result of multiple lytic bone lesions and T12 vertebral collapse. Laboratory work-up showed a serum M protein of 72 g/L and a 24-hour kappa light-chain urine protein excretion of 730 mg, hemoglobin of 10.2 g/dL, serum albumin of 49 g/L, serum β2-microglobulin of 6.4 mg/L, serum creatinine level of 1.6 mg/dL with an estimated glomerular filtration rate (eGFR) of 47 mL/min/1.73 m2, and normal serum calcium and lactate dehydrogenase (LDH) levels. His bone marrow contained 58% plasma cells, which showed the 17p deletion abnormality (Fig 1). He was treated with vertebroplasty and alternating chemotherapy with carmustine, vincristine, cyclophosphamide, melphalan, and prednisone and vincristine, carmustine, doxorubicin and dexamethasone. Because of progressive disease, salvage therapy with bortezomib and dexamethasone was administered with no response. The patient was then switched to lenalidomide and dexamethasone, which yielded minimal response. He underwent autologous stem-cell transplantation (ASCT) with melphalan 200 mg/m2 as high-dose therapy in February 2011, which led to a partial response, but in December 2011, progressive disease was documented, and the patient was enrolled in a clinical trial of carfilzomib monotherapy, with stable disease for 33 cycles. In October 2014 serum M protein rose to 38.6 g/L, with 24-hour kappa light-chain urine protein excretion of 840 mg, serum creatinine of 2.1 mg/dL, and an eGFR of 41 mL/min/1.73 m2. He presented to discuss ongoing treatment options.

Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer

1989 ◽  
Vol 9 (10) ◽  
pp. 4239-4247
Author(s):  
R A Currie ◽  
R G Roeder
Keyword(s):  
B Cell ◽  
Binding Site ◽  
Light Chain ◽  
Specific Binding ◽  
Specific Factor ◽  
Immunoglobulin Gene ◽  
Kappa Light Chain ◽  
Nf Kappa B ◽  
Light Chain Immunoglobulin ◽  
A Site

A 215-base-pair (bp) region of the mouse MOPC 41 kappa light-chain immunoglobulin gene enhancer has been analyzed for specific binding of lymphoid and nonlymphoid nuclear factors. Mobility shift assays with a series of overlapping DNA fragments have mapped DNA-binding sites for three unique factors. The B-cell-specific (OTF-2) and ubiquitous (OTF-1) octamer-binding transcription factors specifically bound to a site centered about 136 bp 5' of the nuclear factor NF-kappa B site. A third specific factor, NF-kappa E, bound to a site that was about 75 bp 5' of the NF-kappa B site and within a region important for enhancer function. This novel factor was found in both mature B and HeLa cell nuclei. B-cell OTF-2, B-cell OTF-1, and HeLa OTF-1 bound to the kappa enhancer and kappa promoter octamer sites with similar affinities despite a 2-bp difference in the kappa enhancer octamer sequence. However, DNase I footprint analyses indicated that affinity-purified OTF-2 bound both to the enhancer OTF site and, surprisingly, to 80 bp of A + T-rich flanking sequence. Moreover, methylation interference studies demonstrated distinct differences in OTF interactions between the consensus octamer in the kappa promoter and the nonconsensus octamer identified in the enhancer. This novel observation of an OTF-binding site in the kappa enhancer provides a common link with the OTF sites in the promoter-proximal regions of all kappa promoters and thus mirrors the structural arrangement of OTF sites found in the promoters and enhancers of immunoglobulin heavy-chain genes.

Early Serum Free Light Chain Responses Following High-Dose Melphalan and Stem Cell Transplantation for AL Amyloidosis Predict Treatment Outcomes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1160-1160
Author(s):  
Vaishali Sanchorawala ◽  
Daniel G. Wright ◽  
Karen Quillen ◽  
Catherine Fisher ◽  
Martha Skinner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Treatment Outcomes ◽  
Light Chain ◽  
Free Light Chain ◽  
High Dose ◽  
Al Amyloidosis ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Treatment Responses ◽  
High Dose Melphalan

Abstract AL amyloidosis is caused by a clonal plasma cell dyscrasia and characterized by widespread, progressive deposition of amyloid fibrils derived from monoclonal Ig light chains, leading to multisystem organ failure and death. Aggressive treatment of AL amyloidosis with high-dose melphalan followed by autologous stem cell transplant (HDM/SCT) can induce hematologic and clinical remissions and extend survival. Several approaches have been used to define hematologic responses following HDM/SCT and other forms of treatment. The standard definition of a hematologic complete response (CR) that we have used requires that there be no evidence of a persistent monoclonal gammopathy by immunofixation electrophoresis (IFE) of serum and urine proteins, or of a persistent plasmacytosis or plasma cell clonality in a bone marrow biopsy by immunohistochemistry. Others have defined hematologic responses according to reductions in free light chain (FLC) measurements. Treatment responses as defined by both criteria correlate with survival and clinical improvement following HDM/SCT. We have carried out a prospective analysis of HDM/SCT treatment outcomes for patients with AL amyloidosis to determine the extent to which early FLC responses within weeks of treatment predict hematologic CR, as defined by our standard criteria. Serum free light chain concentrations (FLC) were measured by a sensitive nephelometric immunoassay in 31 patients with AL amyloidosis, between 2003–2005, 1–3 weeks after treatment with HDM/SCT. Hematologic responses, as defined by standard criteria, as well as FLC responses were subsequently determined at 3, 6 and 12 months. Serum FLC levels or κ/λ FLC ratios were abnormal and informative in 28 patients (90%) prior to HDM/SCT, and these patients were included in subsequent analyses. Twenty patients (71%) achieved normalization of abnormal serum FLC levels or ratios within 1–3 weeks of undergoing HDM/SCT. Of these 20 patients, 13 patients (65%) subsequently achieved a hematologic CR as defined by standard criteria, while 7 (35%) did not, within 3 months following HDM/SCT. In contrast, none of the 8 patients with no demonstrable FLC response within 1–3 weeks of HDM/SCT, were found to have achieved a hematologic CR subsequently. In conclusion, meaningful quantitative FLC responses (or lack of response) can be detected within weeks following HDM/SCT treatment that predict hematologic responses, as defined subsequently by standard criteria based on IFE and marrow studies (p=0.0018 by chi square analysis). Moreover, a lack of an early FLC response predicts for hematologic non-CR. We anticipate that prospective studies of FLC responses in HDM/SCT and other clinical trials for AL amyloidosis will eventually lead to more rapid assessment of treatment responses that will guide therapeutic decisions.

High-Dose Melphalan and Autologous Stem Cell Transplantation in Unusual Non-Amyloid Light Chain Deposition Disorders.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5476-5476
Author(s):  
Karin I. Weichman ◽  
David C. Seldin ◽  
Karen Quillen ◽  
Michael Rosenzweig ◽  
Laura M. Dember ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Light Chain ◽  
Light Chains ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Kappa Light Chain ◽  
Light Chain Deposition

Abstract Light chain deposition disease (LCDD) is caused by a clonal plasma cell disorder in which fragments of monoclonal immunoglobulin light chains, usually with a kappa genotype, are deposited in various tissues in a globular form resulting in organ dysfunction. Crystal-storing histiocytosis (CSH) is another light chain deposition disorder in which monoclonal light chains form intracytoplasmic crystalline deposits. Both LCDD and CSH are uncommon diseases, for which there is limited treatment experience. However, conventional anti-plasma cell chemotherapy with oral melphalan as is used in multiple myeloma has been tried in LCDD with little benefit. Between 1999–2005, five patients with LCDD and one patient with CSH have been treated at Boston University Medical Center with high-dose intravenous melphalan (IVM) followed by autologous peripheral blood stem cell transplantation (SCT). Patients have been treated with either 200mg/m2 of IVM (n=5) or 140 mg/m2 (n=1) depending on age and clinical status and subsequently have been assessed for hematologic responses and for improvements in organ function at 3, 6 and 12 months, and annually thereafter. The median age of patients at the time of treatment has been 45 years (range 34–51). Four patients with LCDD had kappa light chain deposition involving the kidneys and 1 of these patients had extrarenal involvement of the heart on electron microscopy of endomyocardial biopsy as well. One patient with LCDD had lambda deposition involving kidneys only. The patient with CSH had only renal involvement, with kappa light chain plasma cell dyscrasia. All except 1 patient had impaired renal function with creatinine clearance ranging from 21 – 64 ml/min. All treated patients are alive and well at a median follow up of 13.6 months (range 5–24 months). Median survival has not yet been reached. No treatment-related deaths were noted, and treatment-related toxicities were manageable and reversible. All evaluable patients (n=4) have achieved a hematologic complete response of the underlying plasma cell dyscrasia after IVM/SCT. In conclusion, this experience indicates that IVM/SCT is a safe, feasible, and effective modality for the treatment of these unusual light chain deposition disorders.

Sign in / Sign up

Export Citation Format

Share Document