Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis

Hardan, Izhar; Rothman, Rachel; Cohen, Ninette; Shimoni, Avichai; Sokolovsky, Maya; Reichart, M.; Ishoev, Galina; Amariglio, Ninette; Rechavi, Gideon; Nagler, Arnon; Trakhtenbrot, Luba

doi:10.1016/j.exphem.2003.12.001

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…In some patients, a combined morphologic and FISH analysis was performed as recently described. 26 FISH diagnostics were performed either at diagnosis (n ¼ 53) or before allogeneic stem cell transplantation (n ¼ 47). In one patient, FISH analysis was performed on residual myeloma cells after allogeneic stem cell transplantation.…”

Section: Methodsmentioning

confidence: 99%

Impact of genetic abnormalities on survival after allogeneic hematopoietic stem cell transplantation in multiple myeloma

et al. 2008

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We analyzed the prognostic impact of the most frequent genetic abnormalities detected by fluorescence in situ hybridization in 101 patients with multiple myeloma, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after melphalan/fludarabine-based reduced conditioning. The incidences of abnormalities in the present analysis were as follows: del(13q14) (61%), t(11;14)(q13;q32) (14%), t(4;14)(p16.3;q32) (19%), MYC-gain gains (8q24) (21%), del(17p13) (16%) and t(14;16)(q32;q23) (5%). None of the patients had t(6;14)(p25;q32). The overall complete remission (CR) rate was 50% with no differences between the genetic abnormalities except for patients with del(17p13) who achieved less CR (7 vs 56%; P ¼ 0.001). Univariate analysis revealed a higher relapse rate in patients aged 450 years (P ¼ 0.002), patients with del(13q14) (P ¼ 0.006) and patients with del(17p13) (P ¼ 0.003). In multivariate analyses, only del(13q14) (HR: 2.34, P ¼ 0.03) and del(17p13) (HR: 2.24; P ¼ 0.04) significantly influenced the incidence of relapse, whereas for event-free survival, only age (HR 2.8; P ¼ 0.01) and del(17p13) (HR: 2.05; P ¼ 0.03) retained their negative prognostic value. These data show that del(17p13) is a negative prognostic factor for achieving CR as well as for event-free survival after HSCT. Translocation t(4;14) might be overcome by allogeneic HSCT, which will have implication for risk-adapted strategies.

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Section: Methodsmentioning

confidence: 99%

Impact of genetic abnormalities on survival after allogeneic hematopoietic stem cell transplantation in multiple myeloma

et al. 2008

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“…However, the adverse prognostic impact of del (13) has been less pronounced when detected by FISH than when detected by conventional metaphase cytogenetics 1,12,13 and may be related to the potentially greater association between elevated plasma cell proliferation and del(13) detected by metaphase cytogenetics (compared with del(13) detected by FISH), 1,13 or to a high false-positive rate with FISH. 23 Indeed, in a recent review, Stewart and Fonseca 19 highlight that the net effect on prognosis of del (13) is greatest when del(13) is detected by conventional cytogenetics, compared with FISH, and recommend that all multiple myeloma patients be screened for del(13) using conventional cytogenetics.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials

et al. 2006

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In multiple myeloma, deletion of chromosome 13 (del (13)) is associated with poor prognosis regardless of treatment. This study analyzed the impact of del(13) status on response and survival following treatment with either bortezomib or highdose dexamethasone in patients in the SUMMIT and APEX trials. Additionally, matched-pairs subset analyses were conducted of patients with and without del(13), balanced for age and International Staging System parameters. In both SUMMIT and APEX, prognosis appeared to be poorer in bortezomibtreated patients with del(13) compared with patients with no del(13) by metaphase cytogenetics. In the SUMMIT and APEX matched-pairs analysis, response and survival appeared comparable in bortezomib-treated patients with or without del (13) by metaphase cytogenetics. However, patients with del(13) receiving dexamethasone in APEX appeared to have markedly decreased survival compared with those without del(13) by metaphase cytogenetics. These matched-pairs analyses suggest that bortezomib may overcome some of the poor impact of del(13) as an independent prognostic factor. However, sample sizes were very small; these findings require confirmation from further studies. Leukemia (2007) 21, 151-157.

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“…Alternatively, interphase fluorescence in situ hybridization allows detection of residual plasma cells at a lower sensitivity if cytogenetic markers (for example, del(13q14)) are available. 49 A high sensitivity can be achieved by using plasma cell chimerism with real-time PCR based on sequence polymorphisms. 50 The drawbacks of the method are the low specificity and its assessment only after allografting.…”

Section: 2mentioning

confidence: 99%

Mini–Midi–Maxi? How to harness the graft-versus-myeloma effect and target molecular remission after allogeneic stem cell transplantation

Kröger

2007

Leukemia

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Allogeneic stem cell transplantation in multiple myeloma after standard myeloablative conditioning induces a high rate of complete remissions, but long-term freedom from disease is achieved in 30-40% of the cases only. The therapeutic effect of allogeneic stem cell transplantation is due to cytotoxicity of high-dose chemotherapy and immune-mediated graft-versusmyeloma effect by donor T cells. Retrospective studies clearly suggest that both (a) reducing the intensity of high-dose chemotherapy by using reduced-intensity or non-myeloablative conditioning regimen or (b) reducing the immunotherapy of donor T cells by using T-cell depletion result in lower treatmentrelated morbidity and mortality, but also in higher rate of relapse. Therefore, this review will focus on potential strategies of how treatment-related morbidity and mortality might be kept low without an increased risk of relapse and how remission status after transplantation can be enhanced by using the newly established donor immunosystems after allografting as a platform for post-transplant treatment strategies with new drugs (thalidomide, lenalidomide, bortezomib) or immunotherapy (donor lymphocyte infusion, vaccination, tumor-specific T cells) in order to achieve remission on a molecular level, which seems to be a 'conditio sine qua non' to cure myeloma patients.

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Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis

Cited by 14 publications

References 32 publications

Impact of genetic abnormalities on survival after allogeneic hematopoietic stem cell transplantation in multiple myeloma

Impact of genetic abnormalities on survival after allogeneic hematopoietic stem cell transplantation in multiple myeloma

Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials

Mini–Midi–Maxi? How to harness the graft-versus-myeloma effect and target molecular remission after allogeneic stem cell transplantation

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