IgD Multiple Myeloma

Jancelewicz, Z; Takatsuki, Kiyoshi; S, Sugai; Pruzanski, W.

doi:10.1001/archinte.1975.00330010089012

Cited by 155 publications

(25 citation statements)

References 26 publications

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“…MM is associated with a slight male preponderance and a median age at onset of 65-70 years. IgD myeloma accounts for approximately 2-2.6% of patients with myeloma [6,7,8]. …”

Section: Discussionmentioning

confidence: 99%

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Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival

et al. 2016

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Objectives: The long-term clinical characteristics, response to therapy, and survival in patients with immunoglobulin D (IgD) multiple myeloma (MM) were investigated. Methods: A retrospective study was conducted that included 68 patients treated in the last 10 years, 37 of whom received bortezomib only (bortezomib group), 13 of whom received bortezomib and underwent autologous hematopoietic stem cell transplantation (bortezomib + ASCT group), and 18 of whom received conditional chemotherapy (non-bortezomib group). Results: The ratio of males to females was 44:24, and the median age was 56.5 years. The overall response rate of each group was 91.9, 77.8, and 100%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 24 and 15.5 months, respectively, among the 68 patients. The median OS of each group was 23, 21.5, and 27 months, respectively. The median PFS of each group was 18, 12, and 24 months, respectively. The 3- and 5-year OS were 64 and 45%, respectively, and the 3- and 5-year PFS were 39 and 13%, respectively, among the 68 patients. Cox regression showed that the percentage of bone marrow plasmacytosis was significantly associated with OS (p = 0.038). Conclusions: The survival of IgD patients is shorter than that of other MM patients. Treatment strategies with bortezomib followed by stem cell transplantation may boost the response rate and improve survival.

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“…MM is associated with a slight male preponderance and a median age at onset of 65-70 years. IgD myeloma accounts for approximately 2-2.6% of patients with myeloma [6,7,8]. …”

Section: Discussionmentioning

confidence: 99%

“…Jancelewicz et al [7 ]reported a mean survival of 13.7 months in 133 IgD myeloma patients in 1975. Bladé et al [11] reported a median survival of 21 months in 53 IgD myeloma patients, and the proportion of patients alive for 3 and 5 years was 36 and 21%, respectively, in 1994.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival

et al. 2016

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“…It is often associated with relatively high frequencies of renal failure, extra osseous disease, hypercalcemia, amyloidosis and Bence-Jones proteinuria [2-5]. The survival of patients with IgD MM has been reported to be shorter than that of patients with other types of M-protein [2,4,6].…”

Section: Introductionmentioning

confidence: 99%

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

Pisani¹,

Petrucci

Giannarelli³

et al. 2012

J Exp Clin Cancer Res

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BackgroundImmunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes.Design and methodsSeventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group.ResultsMedian age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT.ConclusionsDespite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients.

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“…In humans, IgD myeloma composes only 1 to 2% of all myeloma cases (17). The finding of two patients diagnosed as having IgD-secreting myeloma has provided a rare opportunity to study the DNA rearrangements leading to IgD secretion by these cells at a primary stage of disease.…”

Section: Discussionmentioning

confidence: 99%

“…Also, it has been found that the IgD present on the B-cell surface is primarily associated with K light chains, but the IgD myeloma proteins studied are predominately associated with A light chains. This bias, termed the IgD paradox (17,40), does not exist for other immunoglobulin classes. The IgD paradox further argues against the contention that IgD found in blood serum is merely shed membrane IgD because of its increased susceptibility to proteolysis (16).…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin D switching can occur through homologous recombination in human B cells.

White¹,

Word²,

Humphries³

et al. 1990

Mol. Cell. Biol.

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Prototypical class switching in mouse and human immunoglobulin heavy chains occurs through recombination of tandem blocks of short repeats located 5' to each heavy chain constant region (CH) except C8. Deletion of C, in immunoglobulin D (IgD)-secreting murine plasmacytomas occurs illegitimately. We demonstrate here that in human IgD-secreting myeloma cells freshly isolated from patient bone marrow and in normal peripheral blood B lymphocytes, an IgD switch can occur through homologous recombination of a direct repeat consisting of a 442-bp sequence 1.5 kbp 3' of the JH complex and a 443-bp sequence that is duplicated almost perfectly (96% similarity) 1.7 kbp 5' of the Cc, gene (442/443-base-pair [bp] repeat). This homologous recombination mechanism is not exclusive for IgD switching, since C^deletion endpoints in two established IgD-secreting myeloma cell lines fall outside the 442/443-bp repeat. The 442/443-bp mediated recombination shows cell type specificity, and we propose that it represents a unique mode for increased levels of IgD secretion in humans.The immunoglobulin heavy chain locus is located on chromosome 14 in humans. A heavy chain variable region (VH) gene is composed of one member from each of three gene families designated variable (V), diversity (D), and joining (J). The heavy chain constant region (CH) genes are located downstream of these VH genes in the order C t-CS-Cy3-cyl-C+£-Cal-CyC-y2-cy4-Ce,C.2 (3,12,25). In the primary immune response, the VH gene is transcribed along with the nearest downstream constant region gene, C, , to form a ,u heavy chain mRNA (50). During further B-cell differentiation, however, a given B cell and its progeny may shift from the production of immunoglobulin M (IgM) to one of the other heavy chain isotypes by the expression of downstream CH genes (reviewed in references 28 and 53). Studies primarily with myelomas have indicated that the switch phenomenon is most often the result of an intrachromosomal rearrangement between switch site (S) sequences located upstream of the heavy chain genes. Upon switching, the assembled VDJ gene is brought adjacent to the heavy chain gene to be expressed, resulting in the deletion of the intervening CH genes. Studies, at the DNA sequence level, of mice and humans have demonstrated that these S regions consist of 2 to 10 kilobases (kb) of tandem arrays of repeated sequences (8, 12, 20, 34-36, 41, 42, 48, 56-58). This description of the heavy chain class switch applies to all antibody classes except IgD. To date, the only biological function attributed to IgD with any certainty is serving as an antigen receptor along with IgM on the surface of virgin B cells (22,26,27,33 within the JH-C,, intron some 1.5 kbp 5' of S,, (30).To determine whether either of these sequences is implicated in the secretion of IgD, we have examined primary IgD-secreting myelomas from bone marrow, two established IgD-secreting myeloma cell lines, and normal B lymphocytes from peripheral blood. We found evidence for homologous recombination of the repeat co...

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IgD Multiple Myeloma

Cited by 155 publications

References 26 publications

Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival

Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

Immunoglobulin D switching can occur through homologous recombination in human B cells.

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