Impact of Chromosome 13 Deletion and Plasma Cell Load on Long-Term Survival of Patients with Multiple Myeloma Undergoing Autologous Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5148-5148
Author(s):  
Esbjörn Paul ◽  
Tolga Sutlu ◽  
Evren Alici ◽  
Goesta Gahrton ◽  
Hareth Nahi
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Autologous Transplantation ◽  
High Dose ◽  
Prognostic Impact ◽  
Term Survival ◽  
Chromosome 13 ◽  
First Line Therapy

Abstract High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common treatment for patients under 60–65 years of age with multiple myeloma (MM). In this study, we present a retrospective analysis of the prognostic impact of different factors in patients who have received this treatment as first line therapy in our centre. Abnormalities in chromosome 13 were identified by fluorescence in situ hybridization at the time of diagnosis. The median OS and PFS from transplantation time in the whole group of 193 patients were 90 and 48 months respectively. The median follow-up was 65 months (range: 6–186 months). The complete remission (CR) rate in patients with and without del(13) was 31% and 40% respectively whereas the median OS in patients with del(13) was 58 months but not reached in patients without del(13) (p=0.006). The PFS was 26 months in patients with del(13) and 84 months in those without del(13) (p=0.001). The transplantation related mortality was 2.5% both in the absence and presence of del(13). Patients who achieved CR following ASCT had longer OS and PFS when compared to those who only achieved partial remission. Thus, this study confirms the role of del(13) as a marker of poor prognosis. Multivariate analysis showed that the existence of del(13) was the only single independent factor effecting survival (p=0.001). In patients without del(13), the prognostic impact was even stronger when combined with the plasma cell load in the bone marrow (p=0.020), whereas the plasma cell load had no effect on survival of patients with del(13). Overall, the absence of del(13) in combination with low plasma cell infiltration at diagnosis predicts the best survival.

Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Benefit from the Newer Drugs Used in the Relapsed Setting.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3331-3331 ◽  
Author(s):  
Roman Hajek ◽  
Marta Krejci ◽  
Vlastimil Scudla ◽  
Elena Tothova ◽  
Martin Mistrik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Slovak Republic ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
Term Survival ◽  
Bortezomib Treatment ◽  
High Dose Melphalan

Abstract Background: Autologous stem cell transplantation (ASCT) plays an important role in the treatment of multiple myeloma (MM) patients (pts). In this report, we describe the longterm outcome of cohort of 185 pts with newly diagnosed symptomatic MM treated with ASCT. Median follow-up from the start of therapy was 102.8 months (range 67.2–150.4). We have specifically analyzed benefit from the newer drugs used in the relapsed setting. Methods: A total of 185 MM pts underwent ASCT in the clinical trial 4W of Czech Myeloma Group in 18 centres in Czech Republic and Slovak Republic between 1996 and 2001. The conditioning regimen was high dose melphalan (200mg/m2) in all pts. At diagnosis of MM 72.4% (134/185) of pts had stage III according to Durie- Salmon, 18.4% (34/185) stage II and 9.2% (17/185) stage I. Clinical stages according to ISS were the following: stage 1 in 42.5% (74/174) of pts, stage 2 in 36.8% (64/174) and stage 3 in 20.7% (36/174) pts. Types of monoclonal immunoglobulin were as following: 67.6% (125/185) IgG, 21.1% (39/185) IgA, 9.7% (18/185) light chain, 1.6% (3/185) IgD. Renal insufficiency was presented in 5.9% (11/185) of pts. Median age at transplantation was 54.8 years (range: 28.3–69.2). When the symptomatic relapse of MM after ASCT was occurred, 34.6% (45/130) of pts were treated by conventional chemotherapy (CC) alone, 22.3% (29/130) by thalidomide based regimen, 10.7% (14/130) by bortezomib based regimen, 22.3% (29/130) pts underwent re-transplantation and 10% (13/130) of pts received combination of newer drugs and re-transplantation. Results: Following ASCT, overall response rate (ORR) was 93.5% (173/185), 29.2% (54/185) of pts were in CR, 38.4% (71/185) of pts were in VGPR, 25.9% (48/185) of pts in PR. Median of overall survival (OS) from start of treatment was 77.9 months (9.6 – 147.3), median of TTP was 39.8 months (7.0–146.9). Total of 23.2% (43/185) of pts are alive and disease free, 20.5% (38/185) of pts are alive with relapse and 56.3% (104/185) of pts died with median follow-up 8.3 years from the start of therapy. Significant prognostic parameters for better OS after ASCT were: ISS stage < III (p<0.001), achievement of CR after ASCT (p<0.001) and the use of the newer drugs in the relapsed setting. Patients treated with thalidomide and/or bortezomib comparing to pts treated with CC only had significantly longer survival (p<0.001). Patients treated with re-transplantation only had not better OS (46.1 vs 37.8 months; p=0.224) comparing to pts treated with CC. In opposite, pts treated with the newer drugs and re-transplantation had better prognosis (OS 85.7 vs 37.8 months; p<0.001) than pts treated by CC. In multivariate analysis thalidomide and/or bortezomib treatment in the relapse was the strongest factor for long-term survival (beta 1.988; beta (exp) 7.303; CI: 2.860–18.645; p<0.001) Conclusion: ASCT is effective procedure in MM pts. The achievements CR after transplantation, no presence of stage 3 according to ISS were significant parameters for long-term postransplant survival. Accessibility of the thalidomide and bortezomib was independent of other prognostic factors. The use of the newer drugs in the relapsed setting significantly improved prognosis of patients.

Relapse Rate and Long-Term Survival of AL Amyloidosis Patients Treated with High-Dose Melphalan and Autologous Stem Cell Transplantation (HDM/SCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3094-3094
Author(s):  
David C. Seldin ◽  
Martha Skinner ◽  
Betul Oran ◽  
Karen Quillen ◽  
Kathleen T. Finn ◽  
...  
Keyword(s):  
Median Survival ◽  
Plasma Cell ◽  
Relapse Rate ◽  
Long Term Results ◽  
High Dose ◽  
Al Amyloidosis ◽  
Term Survival ◽  
Long Term Survival ◽  
Early Results

Abstract AL amyloidosis is a plasma cell dyscrasia in which clonal immunoglobulin light chains misfold and are deposited in tissues, leading to organ failure in untreated patients, with median survival of only ~1 year. Oral melphalan and prednisone is minimally effective for the disease, with an increase in median survival to ~1.5 years, and a low rate of hematologic complete responses (CRs). Twelve years ago, we began treating patients with AL amyloidosis with HDM/SCT. In the plasma cell malignancy multiple myeloma, this approach produces hematologic CRs and improves survival, but is not curative, as all patients eventually relapse. In AL amyloidosis, the relapse rate and long-term survival have not been studied, but early results are promising, with most centers reporting CR rates of ~40% and excellent survival in responding patients. To address the durability and long-term results of treatment with HDM/SCT, here we report on the outcome for AL amyloidosis patients treated at Boston Medical Center with HDM/SCT >10 years ago. The first autologous transplant took place on July 18, 1994 in two years, by July 18, 1996, 43 patients with AL amyloidosis without myeloma or other hematologic disease had been treated with HDM/SCT, receiving 100–200 mg/m2 melphalan depending upon age and protocol. Of the 43 patients treated in this 2 yr period, 76% of the patients were male, 81% had a lambda monoclonal disease, and their median age was 52 (range, 29–71). In these first 43 patients, the 100 day peri-transplant mortality rate was 16%. Nineteen of the 43 patients (44%) achieved a hematologic CR after treatment. In annual followup, 4 of 19 patients (21%) eventually relapsed. Fourteen of 43 patients (33%) are still alive; 12 of 19 patients who achieved a CR (63%) are still alive, while only 2 of 34 patients who did not (6%) are still alive. Although there were fewer (8) patients with kappa clonal disease, they had a better outcome, with an 87% CR rate vs. 34% for lambda (P=0.006); 75% of the kappa patients are still alive, vs. 23% of the lambda patients (P=0.005). The median survival of all 43 patients is 4.7 years. Thus, treatment of AL amyloidosis patients with HDM/SCT produces a high CR rate that is durable and is associated with excellent 10 year survival, particularly for those patients achieving a hematologic CR and for patients with kappa clonal disease. Ongoing clinical trials of HDM/SCT, along with strategies to reduce morbidity and mortality and to improve the CR rate, incorporating additional cycles of HDM/SCT or new anti-plasma cell agents, appear to be well-justified by these results.

Long-Term Results in Multiple Myeloma After High-Dose Melphalan and Autologous Transplantation According to Response Categories in the Era of Old Drugs

2014 ◽  
Vol 14 (2) ◽  
pp. 148-154 ◽  
Author(s):  
Massimo Martino ◽  
Maurizio Postorino ◽  
Giuseppe Alberto Gallo ◽  
Giuseppe Messina ◽  
Santo Neri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Long Term Results ◽  
High Dose ◽  
High Dose Melphalan ◽  
Old Drugs

scholarly journals Differences and Similarities in Treatment Paradigms and Goals Between AL Amyloidosis and Multiple Myeloma

Hemato ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 680-691
Author(s):  
Monique C. Minnema ◽  
Rimke Oostvogels ◽  
Reinier Raymakers ◽  
Margot Jak
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Residual Disease ◽  
Intensive Treatment ◽  
High Dose ◽  
Al Amyloidosis ◽  
Treatment Schedule ◽  
Bone Marrow Plasma ◽  
High Dose Melphalan

Although there are similarities in the treatment paradigms between AL amyloidosis and multiple myeloma, there are also fundamental differences. A similarity is of course the use of anti-plasma cell drugs in both diseases; however, the most serious mistake a hemato-oncologist can make is to use the same treatment schedule in dosing and frequency in AL amyloidosis patients as in multiple myeloma patients. AL amyloidosis patients with >10% bone marrow plasma cell infiltration in particular are at risk of receiving a more intensive treatment than they can tolerate. This difference in dosing and frequency is true for many anti-clonal drugs, but it is most apparent in the use of high-dose melphalan and autologous stem cell transplantation. While in multiple myeloma in the age group of ≤70 years, more than 80% of patients are fit enough to receive this intensive treatment, this is the case in less than 20% of AL amyloidosis patients. A similarity is the alignment in the goal of treatment. Although in AL amyloidosis has long been recognized that the goal should be complete hematological remission, this has become more apparent in multiple myeloma in recent years. A common goal in the coming years will be to evaluate the role of minimal residual disease to improve survival in both diseases.

scholarly journals Allogeneic Stem Cell Transplantation in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Christine Greil ◽  
Monika Engelhardt ◽  
Jürgen Finke ◽  
Ralph Wäsch
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Groups ◽  
High Dose ◽  
Term Survival ◽  
Hematopoietic Stem

The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.

The role of complete response in multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (15) ◽  
pp. 3139-3146 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact ◽  
Good Partial Response

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.

scholarly journals Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma

Haematologica ◽  
2007 ◽  
Vol 92 (10) ◽  
pp. 1399-1406 ◽  
Author(s):  
H. J.K. van de Velde ◽  
X. Liu ◽  
G. Chen ◽  
A. Cakana ◽  
W. Deraedt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
High Dose Therapy ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Survival ◽  
Dose Therapy
Sign in / Sign up

Export Citation Format

Share Document