Once Weekly Bortezomib (Velcade) Preserves Bone Health by a Direct Effect on Osteoclast Function Independent of Its Effect on the Malignant Plasma Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3458-3458
Author(s):  
Shachar Peles ◽  
Nicholas M. Fisher ◽  
Feng Gao ◽  
Steven M. Devine ◽  
Michael H. Tomasson ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Disease Progression ◽  
Patient Population ◽  
Plasma Cells ◽  
Bisphosphonate Therapy ◽  
Bone Lesions ◽  
Specific Marker ◽  
Serum Osteocalcin ◽  
Post Transplant ◽  
Osteoclast Function

Abstract Bone resorption is increased in multiple myeloma (MM) due to increased osteoclast activity leading to osteoporosis and osteolytic bone lesions. Assays of urinary excretion of N-telopeptide (NTX), a highly specific marker of bone resorption, decrease by 20–70% following treatment with bisphosphonates. Receptor activator of NF-kB (RANK) ligand increases osteoclast mediated bone resorption in part through activation of nuclear factor kappa-B(NF-kB). Preclinical studies have shown bortezomib to decrease osteoclast function through inhibition of NF-kB. However, no clinical data exists on the effect of bortezomib on markers of bone resorption. We designed a prospective clinical trial aimed at measuring the effect of bortezomib on urinary NTX excretion and serum osteocalcin levels in patients with MM. Patients received six cycles of consolidation bortezomib 1.3mg/m2 given once weekly (for ease of administration) for 4 of every 5 weeks, 90–120 days post transplant. Urinary NTX excretion and serum osteocalcin were measured on day 1 of cycles 1, 2 and 3 of therapy. Treatment with bisphosphonates was prohibited from 42 days prior to stem cell collection and until cycle 3 of post transplant bortezomib therapy. To date, 31 of 40 enrolled patients have proceeded to receive bortezomib consolidation therapy and are evaluable for markers of bone metabolism. Characteristics of the patient population and disease include (no. of patients): male (21), female (10), median age 56 years (range 39–70), Stage II (8), Stage III (23), IgG (20), IgA (9), free light chain (2). The median duration between discontinuation of prior bisphosphonate therapy and initiation of post transplantation weekly bortezomib was 158 days (Range 132–196). Of the 19 patients who have completed all 6 prescribed cycles of consolidation bortezomib, only one patient has had a 50% or greater reduction in paraprotein, 16 had stable disease and 2 had disease progression. Nevertheless, excretion of NTX decreased by a mean of 7.4 nmol/mmol creatinine over each 5 week treatment cycle (p=0.007) with a mean decline of 33% over baseline values after 2 cycles of consolidation, once weekly bortezomib therapy (see table). Only one patient displayed an increase in urinary NTX of greater than 30%. This was the only patient with evidence of disease progression during this period of consolidation. Contrary to preclinical and clinical reports of proteasome inhibition resulting in increased osteoblastic bone formation, a decrease was seen in serum osteocalcin. This data suggests that bortezomib, given just once weekly, has a substantial inhibitory effect on osteoclastic bone resorption in MM even in the absence of effects on the malignant plasma cells. The magnitude of effect appears comparable to that achieved with bisphosphonates. Given concerns regarding long term toxicities of bisphosphonate therapy, including nephrotoxicity and osteonecrosis of the jaw, bortezomib may represent an alternative agent effective in controlling both the myeloma and bone disease in this patient population. Cycle 1 Day 1 Cycle 2 Day 1 Cycle 3 Day 1 Mean Change p value Mean Osteocalcin (Range)(ng/ml) 28.16 (9.30 – 81.90) (n = 28) 26.69 (9.50 – 57.40) (n = 25) 26.12 (11.60 – 73.00) (n = 21) −4.6 (16%) 0.02 Mean NTX excretion (Range)(nmol/mmol Cr) 44.87 (10 – 121) (n = 23) 36.00 (7 – 65) (n = 24) 30.43 (9 – 87) (n = 21) −14.8 (33%) 0.007

A prospective study of the effects of once weekly bortezomib on markers of bone metabolism in patients with multiple myeloma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7548-7548 ◽  
Author(s):  
S. Peles ◽  
N. M. Fisher ◽  
F. Gao ◽  
M. H. Tomasson ◽  
J. F. Dipersio ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Plasma Cells ◽  
Proteasome Inhibition ◽  
Inhibitory Effect ◽  
Osteonecrosis Of The Jaw ◽  
Bone Lesions ◽  
Consolidation Therapy ◽  
Alternative Agent ◽  
Osteoclast Function ◽  
A Prospective Study

7548 Background: Increased osteoclast activity in MM leads to bone resorption, osteoporosis and osteolytic bone lesions. Urinary excretion of N-telopeptide (NTX), a marker of bone resorption, decreases by 20–70% following treatment with bisphosphonates. Preclinical studies have shown bortezomib to decrease osteoclast function through inhibition of NF-kB. However, no clinical data exists on the effect of bortezomib on markers of bone resorption. Methods: Six cycles of consolidation bortezomib 1.3mg/m2 were given once weekly for 4 of every 5 weeks, 90–120 days post transplant. Urinary NTX excretion and serum osteocalcin were measured on day 1 of cycles 1, 2 and 3 of therapy. Bisphosphonates were prohibited from 42 days prior to stem cell collection and until cycle 3 of consolidation therapy. Results: 33 of 40 enrolled patients received bortezomib consolidation. Patient population and disease characteristics (no. of patients): male (22), female (11), median age 56 years (range 39–70), Stage II (9), Stage III (24), IgG (22), IgA (9), free light chain (2). The median duration between discontinuation of bisphosphonates and initiation of consolidation bortezomib was 158 days (Range 110–196). Only one patient had a >50% reduction in myeloma paraprotein. Nevertheless, excretion of NTX declined by a mean of 32% over baseline values after 2 cycles of consolidation therapy. The only patient with an increase in NTX of >30% was also the only patient with evidence of disease progression during this period of therapy. Contrary to reports of proteasome inhibition resulting in increased osteoblastic bone formation, a decline was seen in osteocalcin. Conclusions: Bortezomib has an inhibitory effect on osteoclastic bone resorption in MM similar to that with bisphosphonates even in the absence of effects on malignant plasma cells. Bisphosphonates may result in nephrotoxicity and osteonecrosis of the jaw and bortezomib represents an alternative agent that may control both the myeloma and bone disease. [Table: see text] No significant financial relationships to disclose.

Engraftment Syndrome Is Common in Patients with POEMS Syndrome Undergoing PBSCT.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2995-2995
Author(s):  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
Shaji K. Kumar ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Volume Overload ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Post Transplant ◽  
Gm Csf ◽  
Engraftment Syndrome ◽  
Sclerotic Bone Lesions ◽  
Definition Of ◽  
Discharge From Hospital

Abstract Background: POEMS syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis, & high VEGF. We noted an unexpectedly high transplant related morbidity, which we have since postulated to be ES. Methods: 30 patients with POEMS were treated with PBSCT at Mayo Clinic Rochester. We retrospectively studied outcomes, with an emphasis on treatment related morbidity. Two definitions of ES were used: Spitzer (BMT 2001) and Maiolino (BMT 2003). Results: Two-thirds were male. Median age was 48, range 20–70. Time from first symptoms and diagnosis was 26 and 4 months, respectively. To mobilize stem cells, CTX/G-CSF was used in 5 & G-CSF in the remainder. Conditioning was Mel200 (n=19), Mel140 (n=10), and BEAM (n=1). Post-transplant 15 had GM-CSF begun day+6. Only 10% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0–175). Factors predicting for later dismissal included age (p=0.04), abnormal CXR 7 to 17 days post transplant (p<0.0001), & bolus corticosteroids (CS) beyond day 12 post-transplant (p=0.006). Ninety-three percent had fever, although only 9 had bacteremia. Eight satisfied criteria for ES according to Spitzer and 14 according to Maiolino. Another 3 patients received steroid bolus days 8, 12, and 11 for presumed ES but did not meet criteria because of delayed ANC recovery (days 16, 18, and 20, respectively). Of the 5 patients requiring endotracheal intubation, 3 satisfied Maiolino’s criteria for ES. Although these 3 received bolus CS during their course, administration was delayed at 18, 14, and 18 days. The patient whose CS bolus antedated intubation only received prednisone 30 mg/day. In toto, fourteen patients received bolus CS (daily doses between 20 and 1200 mg prednisone equivalents) commencing day 8 to 59. Those 7 patients who received CS before day 13 did better than the 7 who received them day 13 or later (Table). Conclusions: It is essential to recognize that nearly 50% of patients satisfied formal criteria for ES as defined by Maiolino. In these patients ES may run a self-limited course or lead to catastrophe. No Steroid (n=16) Steroid ≤ D12 (n=7) Steroid > D12 (n=7) P *Engraftment syndrome according to definition of Maiolino (M) or of Spitzer (S). ES M / S, n* 5 / 2 4 / 4 5 / 2 NA Wt change, % 0.6 (−.4.2–6.7) 6.7 (3.6–27.2) 11.2 (–2.1–23.2) 0.005 Rash, % 27 71 43 0.13 Diarrhea, % 73 86 86 0.71 Tmax, C 39 (37.8–41) 40.1 (39–41.1) 38.9 (38.7–40.8) 0.08 1st fever, day 10 (6–15) 8 (7–9) 12 (8–146) 0.007 Abn CXR1, % 13 71 71 0.03 Ventilator, % 0 14 71 0.004 First WBC, day 12 (8–21) 14 (12–14) 14 (12–17) 0.03 ANC500, day 15 (12–29) 16 (14–115) 18 (15–45) 0.08 PLT20, day 12 (8–41) 20 (11–115) 24 (9–170) 0.05 PLT50, day 15 (11–192) 32 (16–115) 56 (13–551) 0.03 RBCs, units 3 (2–8) 6 (4–31) 11 (6–64) 0.0008 PLTS, aph. units 2 (1–9) 9 (4–51) 18 (4–60) 0.0004 Hosp dsm, day 15 (13–36) 21 (15–69) 41 (16–175) 0.009

Whole Genome Sequencing Illuminates the Genetic and Biological Features Underlying the Transition of SMM to MM

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 296-296
Author(s):  
Brian A Walker ◽  
Christopher P Wardell ◽  
Lucía López-Corral ◽  
Sean Humphray ◽  
Lisa Murray ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Disease Progression ◽  
Genome Sequencing ◽  
Plasma Cells ◽  
Cell Leukaemia ◽  
Bone Lesions ◽  
Whole Genome ◽  
Essential Components ◽  
Clinical Stages ◽  
Genetic Events

Abstract Abstract 296 A well defined model of disease progression has been established in myeloma based on the transition of normal plasma cells to monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma (SMM), myeloma (MM) and finally to plasma cell leukaemia. The most likely mechanism underlying the initiation and progression of myeloma is that the primary genetic events, such as IGH translocations or hyperdiploidy confer a proliferative/survival advantage but not a truly malignant phenotype. Subsequently, these cells acquire secondary genetic aberrations that are associated with uncontrolled proliferation and invasion which manifest as bone lesions and myelosuppression. We have addressed the hypothesis that we can gain critical understandings of the mechanisms leading to disease progression, by defining the different genetic events present in the early pre-clinical stages of the disease (SMM) compared to those present in the clinical stages of the disease (MM). One of the essential components of disease progression is the acquisition of novel genetic hits and clonal selection based on the selection and expansion of the subclone most able to survive. We hypothesise that within the malignant plasma cells there is substantial clonal heterogeneity and that at different stages of the disease the extent of this is variable, with progression occurring in an oligoclonal fashion by acquisition of multiple genetic hits rather than as a result of the linear acquisition of sequential genetic hits. In this study we utilized massively parallel sequencing to study paired plasma cells from 2 patients who had progressed from SMM to MM and compared them to the patients non-involved DNA. Patients had been diagnosed with SMM, and had a bone marrow aspirate taken, at least 18 months prior to being diagnosed with MM. Both samples were taken before the patient underwent any treatment. The 2 patients were analyzed at the two time points and compared to the germline DNA obtain from the peripheral blood sample, using whole genome sequencing to identify acquired single nucleotide variants (SNVs), indels and translocations in the SMM and MM samples. Additionally, changes acquired at the transition from SMM to MM were examined along with frequency of abnormal reads at these sites. 100 ng genomic DNA from CD138 MACsorted cells and normal white cells was sequenced using 75 bp paired-end reads on a GAIIx (Illumina) to a median depth of 32x and 98% at 1x and 84% at 20x coverage. Data were aligned to the human genome (hg19) using ELAND v2e and acquired SNVs and indels called using CASAVA 1.8. In both samples the majority of SNVs were found in intergenic (range 64–71%) or intronic (25–31%) regions. The number of acquired SNVs within exons (including UTRs) accounted for only 0.5–1.1% of all variants. There was no statistical difference in the genomic distribution of SNVs between SMM and MM samples. Analysis of the SMM and MM samples shows that SNVs in the MM sample, which are acquired in the tumour, are all present in the SMM sample albeit at lower levels, indicating that the dominant MM clone was always present before transformation from SMM. Additionally, there are SNVs present in the SMM sample which are not found in the MM sample from the same individual. For example, variant calls can be detected at an incidence of 11–15% in the SMM sample and are undetected in the MM sample, at this sequencing depth. Acquired indels were found almost exclusively (>99%) within intergenic and intronic regions in both SMM and MM samples. As with the SNVs, all indels found in the MM samples were also found in the SMM sample from the same patient, but not all indels found in the SMM sample were found in the MM sample. The results presented indicate that during the progression from SMM to MM there is an oligoclonal selection process which results in the emergence of a dominant clone, and other sub-clones containing non-advantageous passenger mutations are not selected. Any of these SMM clones can clearly and rapidly transform to MM with full malignant potential. Therefore, targeted therapeutic approaches aimed at mutations in the MM dominant clone may not be curative, but may allow the propagation of minor clones without these mutations. It is therefore imperative to determine which mutations are present in pre-malignant clones to establish a clinical course of action in treatment. Disclosures: Humphray: Illumina: Employment. Murray:Illumina: Employment. Ross:Illumina: Employment. Bentley:Illumina: Employment.

A Long-Term Study of Prognosis on Monoclonal Gammopathy of Undetermined Significance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4994-4994
Author(s):  
Delvyn Caedren Case ◽  
Marjorie A. Boyd
Keyword(s):  
Bone Marrow ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphocytic Leukemia ◽  
Bone Lesions ◽  
Monoclonal Protein ◽  
Long Term Study ◽  
Progression Of Disease ◽  
Undetermined Significance

Abstract From 1976 to 2006, 547 patients have been identified and followed for monoclonal gammopathy of undetermined significance (MGUS). Criteria of inclusion included presence of serum monoclonal protein of a concentration of 2 g per deciliter or less; no or moderate amounts of monoclonal light chains in the urine; the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and proportion of plasma cells in the bone marrow of 5% or less. Patients identified as MGUS were followed every 6 months with physical examination, CBC, chemistries, and paraprotein studies. Ages ranged from 32 – 100 years (median 70 years). There were 214 males and 333 females. Over the 30 years of observation, 61 patients have developed disease progression: myeloma 29, lymphoma 12, macroglobulinemia 10, chronic lymphocytic leukemia 7, and amyloid 3. Time to develop myeloma ranged from 2–24 years (median 6 years), macroglobulinemia 2–8 years (median 5 years), and amyloid 3–10 years (median 10 years). Patients developed myeloma throughout the entire period of observation: 2, 3, 3, 4, 4, 4, 4, 5, 5, 5, 6, 6, 6, 6, 6, 7, 7, 8, 8, 9, 10, 10, 11, 14, 15, 15, 18, 20, and 24 years. Survival from diagnosis of myeloma was 1+ – 14+ months (median 36 months) for myeloma and 24 – 108+ months (median 48 months) for macroglobulinemia. The only reliable method of identifying progression of disease to myeloma/macroglobulinemia/amyloid was serial determinations of paraprotein level. In this large series followed for 30 years, with a more restricted diagnosis of MGUS (paraprotein level ≤ 2 g per deciliter and 5% or less bone marrow plasma cells), 1% of all patients identified developed progression of disease. No patient developed disease progression in less than 2 years using the more restricted diagnosis. Risk of progression increased with time with patients developing myeloma even 20 years or longer of follow-up. Serial evaluations of paraprotein levels are indicated in patients identified as MGUS.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

scholarly journals AB0781 ONE, NONE, MANY: REFLECTIONS ON A RARE CASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1416.2-1416
Author(s):  
G. Sandri ◽  
L. Belletti ◽  
M. Cavedoni ◽  
C. Galluzzo ◽  
S. Bruni ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Autoimmune Diseases ◽  
Short Stature ◽  
Rare Diseases ◽  
Bone Development ◽  
Therapeutic Interventions ◽  
Cardiac Conduction ◽  
Bone Lesions ◽  
The European Union ◽  
Early Puberty

Background:Rare diseases are all those diseases that present, in the European Union, a prevalence of less than 5 cases per 10,000 people. The number of rare diseases is estimated at roughly 7,000 but there are also longstanding medical conditions that elude diagnosis and could be identified as rare.Objectives:Demonstrate the importance of international research in orphan diseases.Methods:We report a case of 44 y/o female patient who arrived to our observation in 2006. Short stature, early puberty, ligament laxity, BMI <17. From the age of 29: recurrent diarrhea, pain in the spine, osteolytic lesions in spine and endosteal thickening in long bones, muscle contractures, strength deficit, muscular hypotrophy and hypotonia, cardiac conduction and blood pressure disorders, demyelinating MS-lesions, hyperprolactinaemia, slow wound healing, sicca syndrome, osteoporosis. No familiarity for bone lesions. In 2007 her first son (21y/o) began to complain pain at limbs. The young man presented the same bone lesions as the mother and shortening of the PR, prolactinoma, recurrent diarrhea, short stature, early puberty. Over the years numerous pathologies have been first hypothesized and then excluded: multiple sclerosis, bone metastases, Paget’s disease, celiac disease, McCune Albright, Camurati-Engelmann syndrome, mitochondrial disease. No conclusive diagnosis despite the thousands of kilometers traveled, the numerous experts heard and the countless examinations carried out by the patients.Results:In September 2009, the patients had been investigated at the NIH (Washington D.C.) during the “Undiagnosed Diseases Program” but without results until 2013 when the patients were informed of the detection of an ATP6V1H gene mutation never described before in humans. The gene encodes a vacuolar ATPase, a multimeric enzyme that plays several roles: is involved in endocytosis, intracellular trafficking, and protein degradation and energy production, appears to be a risk factor in the development of dyslipidemias and type II diabetes, has a bone resorption function. Also in the patient’s father were founded the same mutation and asymptomatic bone lesions. In 2016 and 2017 studies have reported mouse models of osteoporosis that were generated by knocking out the ATP6V1H gene.Conclusion:from this case it is possible to understand the difficulty of diagnosing a rare disease, the need of an international collaboration in research. From these studies it can be deduced moreover that the ATP6V1H gene could be an important target for therapeutic interventions aimed at preventing bone resorption and treating osteoporosis; evidence to support exploration of MMP9 and MMP13 as therapeutic targets for patients with ATP6V1H deficiency.This mutation seems to affect only one family, but it is possible that the penetrance of the disease-causing mutation is variable. In literature is reported an enhanced expression of MMP-9 in a variety of autoimmune diseases and neurological pathologies (2) therefore the mutation can be at the basis of other much more common pathologies.References:[1]Zhang Y, Huang H, Zhao G, Yokoyama T, Vega H, Huang Y, Sood R, Bishop K, Maduro V, Accardi J, Toro C, Boerkoel CF, Lyons K, Gahl WA, Duan X, Malicdan MC, Lin S. ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13. PLoS Genet. 2017 Feb 3;13(2):e1006481. doi: 10.1371/journal.pgen.1006481.[2]Ram M, Sherer Y, Shoenfeld Y. Matrix metalloproteinase-9 and autoimmune diseases. J Clin Immunol. 2006 Jul;26(4):299-307. doi: 10.1007/s10875-006-9022-6.Disclosure of Interests:Gilda Sandri: None declared, Lorenza Belletti: None declared, Michele Cavedoni: None declared, Claudio Galluzzo: None declared, stefano bruni Consultant of: Genzyme, Employee of: Genzyme, Maria Teresa Mascia: None declared

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

scholarly journals The Evolution in The Treatment of Multiple Myeloma Towards Targeted Magnetic Molecularly Imprinted Nanomedicines

2015 ◽  
pp. 1-2
Author(s):  
Edgar Pérez-Herrero
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bacterial Infections ◽  
Plasma Cells ◽  
The Body ◽  
Western World ◽  
Bone Lesions ◽  
Non Hodgkin Lymphoma ◽  
Clonal Proliferation ◽  
Tract Infections

Multiple myeloma is the second more frequently haematological cancer in the western world, after non-Hodgkin lymphoma, being about the 1-2 % of all the cancers cases and the 10-13% of hematologic diseases. The disease is caused by an uncontrolled clonal proliferation of plasma cells in the bone marrow that accumulate in different parts of the body, usually in the bone marrow, around some bones, and rarely in other tissues, forming tumor deposits, called plasmocytomas. This uncontrolled clonal proliferation of plasma cells produces the secretion of an abnormal monoclonal immunoglobulin (paraprotein or M-protein) and prevents the formation of the other antibodies produced by the normal plasma cells that are destroyed. The anormal secretion of paraproteins unbalance the osteoblastosis and osteoclastosis processes, leading to bone lesions that cause lytic bone deposits and the release of calcium from bones (hypercalcemia) that may produce renal failure. Regions affected by bone lesions are the skull, spine, ribs, sternum, pelvis and bones that form part of the shoulders and hips. The substitution of the healthy bone marrow by infiltrating malignant cells and the inhibition of the normal production of red blood cells produce anaemia, thrombocytopenia and leukopenia. Multiple myeloma patients are immunosuppressed because of leukopenia and the abnormal immunoglobulin production caused by the uncontrolled clonal proliferation of plasma cells, being susceptible to bacterial infections, like pneumonias and urinary tract infections. The interaction of immunoglobulin with hemostatic mechanisms may lead to haemorrhagic diathesis or thrombosis. Also, disorders of the central and peripheral nervous system are part of the disease, being the more common neurological manifestations the spinal cord compressions and the peripheral neuropathies.

scholarly journals Production of interleukin-1 by bone marrow myeloma cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 380-387 ◽  
Author(s):  
F Cozzolino ◽  
M Torcia ◽  
D Aldinucci ◽  
A Rubartelli ◽  
A Miliani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Interleukin 1 ◽  
Long Bone ◽  
Bone Lesions ◽  
Normal Donor ◽  
Biologic Activity ◽  
Culture Supernatants

Plasma cells isolated from bone marrow (BM) aspirates of 12 patients with multiple myeloma (MM) and nine patients with monoclonal gammopathy of undetermined significance (MGUS) were analyzed for production of cytokines with bone-resorbing activity, such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and lymphotoxin (LT). Culture supernatants of plasma cells from MM, but not from MGUS or normal donor, invariably contained high amounts of IL-1-beta and lower amounts of IL-1-alpha. With a single exception, TNF/LT biologic activity was not detected in the same supernatants. IL-6 was present in two of five supernatants tested. Normal B lymphocytes released both IL-1 and TNF/LT activities for four days after activation in vitro; however, production of these cytokines ceased at the final stage of plasma cell. Unexpectedly, the mRNA extracted from MM plasma cell hybridized with TNF- and LT- specific, as well as IL-1-specific probes, although the culture supernatants did not contain detectable TNF/LT biologic activity. When tested in the fetal rat long bone assay, MM plasma cell supernatants displayed a strong osteoclast-activating factor (OAF) activity, which was greatly reduced but not completely abolished by neutralizing anti- IL-1 antibodies. Anti-TNF or anti-LT antibodies were ineffective in the same test. We conclude that the IL-1 released in vivo by malignant plasma cells has a major role in pathogenesis of lytic bone lesions of human MM.

Sign in / Sign up

Export Citation Format

Share Document