Multi-Organ Involvement of Multiple Myeloma Cells In the Cases of Recent 10 Years: A Clinicopathologic Study of 81 Consecutively Autopsied Cases

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5004-5004
Author(s):  
Shotaro Hagiwara ◽  
Makoto Mochizuki ◽  
Hisako Endo ◽  
Risen Hirai ◽  
Akira Tanimura ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Clinicopathological Feature ◽  
Pathological Feature ◽  
Myeloma Cells ◽  
The Impact

Abstract Abstract 5004 Background: Despite recent progress in treatment, multiple myeloma is still uncurable disease. The impact of modern therapy on the causes of death and pathological feature of end-stage myeloma is not fully understood. Methods: We studied autopsied cases with multiple myeloma between 1979 and 2009 at National Medical Center of Global Health and Medicine, Tokyo, Japan. We compared the clinicopathological feature of the autopsied cases in recent 10 years with the cases before 2000. Statistical analysis was performed using student's t-test and chi-square test. Results: There were 81 autopsied cases between 1979 and 2009. 31 cases were autopsied in recent 10 years and the older 50 cases were before 2000. Mean age at death was 59.2 and 65.1 years old, and the mean duration of illness was 46.1 and 31.9 months, respectively. Stem cell transplantation was performed in 13 (12 autologous, 1 allogeneic) of recent cases and 3 (2 autologous and 1 allogeneic) of older cases. In recent cases, five patients were treated with bortezomib, 2 were with thalidomide and 2 were with both. Extramedullary infiltration of myeloma cells were observed in both groups. The frequent sites of involvement were spleen, liver, kidney, lymph nodes, lung, pancreas, adrenal gland and perioneum. The infiltration in liver and lung was significantly frequent in the recent cases than in the older cases (58.1% vs. 28.0%, p=0.007, and 38.7% vs. 18%, p=0.039). Infection as a cause of death was noted more frequently in the recent cases than in the older cases (41.9% vs. 18.0%, p=0.019). Amyloid deposition was detected in 16.1% and 22.0% (ns.), and myeloma kidney was noted in 48.4% and 60% (ns.). Conclusion: High dose chemotherapy with stem cell support and novel agents have been contributed to improving the survival. However, the increase in resistant bacterial and fungal infection is serious problem. Also, extramedullary relapse after autologous and allogeneic stem cell transplantation is not rare, and extramedullary progression under thalidomide has been reported. In our recent autopsied cases, the incidence of fatal infection and extramedullary involvement of myeloma cells was significantly higher than in the older cases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Stem Cell Transplantation in Multiple Myeloma

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 311-316 ◽  
Author(s):  
Michel Attal ◽  
Philippe Moreau ◽  
Herve Avet-Loiseau ◽  
Jean-Luc Harousseau
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Dose Intensity ◽  
Hematologic Malignancies ◽  
Common Disease ◽  
High Dose ◽  
The Impact ◽  
Proof Of Efficacy

AbstractMultiple myeloma (MM) is one of the key hematologic malignancies in which the impact of dose intensity has been demonstrated. Consequently, in 2005, MM was the most common disease for which autologous stem cell transplantation (ASCT) was indicated both in Europe and in the U.S. However, ASCT is not curative, and most patients relapse within a median of 3 years. Novel agents such as thalidomide (Thalidomid), bortezomib (Velcade), or lenalidomide (Revlimid) have been introduced to improve high-dose therapy, and promising results have been reported. Conversely, results from myeloablative allogeneic stem cell transplantation remain disappointing due to high transplantation-related mortality, justifying the exploration of strategies such as reduced-intensity conditioning, which have been shown to be feasible but for which proof of efficacy requires continued study.

Pretransplant hemoglobin and serum creatinine levels correlate with progression free survival in myeloma patients undergoing autologous stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19532-e19532
Author(s):  
Taner Demirer ◽  
Guldane Cengiz Seval ◽  
Selami Kocak Toprak ◽  
Sinem Civriz Bozdag ◽  
Meltem Kurt Yuksel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Serum Creatinine ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
The Impact

e19532 Background: High dose melphalan and autologous stem cell transplantation (ASCT) significantly prolong survival for patients with multiple myeloma (MM). The purpose of this study is to assess the effects of hemoglobin (Hgb) and serum creatinine (Crea) values at the time of transplantation on the overall outcome of patients with multiple myeloma treated at our transplant center. Material & Methods: This analysis included 247 consecutive patients who underwent ASCT for MM between 2010-2016. Hemoglobin was grouped as low or high relative to their sample median. Patients were also stratified according to serum Crea value at the time of transplantation ( < 2 or ³2 mg/dl). Results: The median age was 57 (29-75) years and most patients were male (n = 151, 61.1%), IgG subtype (n = 124, 50.2%), and ISS stage 3 (n = 122, 49.4%). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). The most commonly induction regimens included VAD (vincristine, doxorubicin and dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), respectively. Since maintenance was not an approved treatment in myeloma most patients did not receive any. For the entire cohort, the median Hgb and Crea were 11.5 g/dL and 0.9 mg/dL respectively. No difference in progression free survival (PFS) was observed between a lower and higher Hgb (82 vs. 81 months, p = 0.96). However, the median PFS was significantly longer in patients with a lower Crea compared to those with a higher Crea (83 vs. 48 months, p = 0.01). Patients with both a lower hemoglobin and higher Crea experienced shorter PFS compared to those with a higher hemoglobin and lower Crea (45 vs. 82 months, p < 0.001). We failed to demonstrate the impact of creatinin levels on time to neutrophil and platelet engraftment. There were no differences in OS according to lower vs. higher Hgb (58 vs. 52 months; p = 0.29, respectively) but in higher crea cohort worse OS was observed (41 months vs. 57 months; p = 0.02, respectively). Conclusions: We demonstrate that hemoglobin and creatinine represent important determinants of clinical outcomes after ASCT. A lower hemoglobin and higher creatinine, individually and when combined, were associated with shorter PFS. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant Hgb and Crea levels on ASCT outcomes.

scholarly journals Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Drug Induction: A Retrospective Single-Center Analysis

2017 ◽  
Vol 137 (3) ◽  
pp. 163-172 ◽  
Author(s):  
Gabriela B. Thoennissen ◽  
Dennis Görlich ◽  
Ulrike Bacher ◽  
Thomas Aufenberg ◽  
Anne-Christin Hüsken ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Staging System ◽  
High Dose ◽  
Single Center ◽  
The Impact

Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0.03) and stage 3 according to the International Staging System (p = 0.006) as adverse risk factors regarding PFS. Median OS was significantly better in newly diagnosed MM patients receiving induction therapy with novel agents, e.g., bortezomib, thalidomide, or lenalidomide, compared with a traditional regimen (69 vs. 58 months; p = 0.01). More patients achieved at least a very good partial remission in the period from 2005 to 2012 than from 1996 to 2004 (65 vs. 30%; p < 0.001), with a longer median OS in the later period (71 vs. 52 months, p = 0.027). In conclusion, our analysis confirms HDCT-ASCT as an effective therapeutic strategy in an unselected large myeloma patient cohort with a low TRD rate and improved prognosis due to novel induction strategies.

The Reason Why High-Dose Melphalan Followed by Autologous Stem-Cell Transplantation Produces Good Response in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5201-5201
Author(s):  
Yoshiaki Kuroda ◽  
Akira Sakai ◽  
Yoshiko Okikawa ◽  
Shoso Munemasa ◽  
Yuta Katayama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cells ◽  
High Dose ◽  
Myeloma Cells ◽  
Before And After ◽  
High Dose Melphalan

Abstract Multiple myeloma (MM) is the result of a clonal proliferation of plasma cells. And myeloma cells have been shown to be heterogeneous with regard to their morphology and biological character. Recently, correlations between molecular subtypes and prognosis have been identified as a good prognosis with t(11;14) and a poor prognosis with t(4;14) and t(14;16) besides chromosome 13 abnormalities. But it is still unclear how those molecular events work on the prognosis of MM patients. And it is difficult to find the heterogenesity of myeloma cells in each MM case by molecular analysis. Twenty years ago Greipp et al. classified myeloma cells as mature, intermediate, immature and plasmablastic type, and then they showed that plasmablastic morphology is an independent predictor of poor survival rate after autologous stem-cell transplantation. On the other hand, Kawano et al. classified myeloma cells into three types by their phenotype (Huang N, Blood82: 3721, 1993, Kawano MM, Blood82: 564, 1993); immature (MPC1−, CD49e−, CD45−/+), intermediate (MPC1+, CD49e−, CD45−), and mature (MPC1+, CD49e+/−, CD45+). This classification according to the phenotype is good correlation with that by morphology. And they indicated that immature myeloma cells have activity of proliferation. We analyzed both phenotypic and morphological findings of myeloma (plasma) cells consecutively before and after chemotherapy in 23 MM cases in order to find what kind of drug might be useful to reduce the main population of heterogeneous myeloma cells. The phenotypic and morphological analysis were performed before and after ten-cycles of melphalan-predonine (MP) in 2 cases, three or four-cycles of vincristine-doxorubicin-dexamethasone (VAD) in 10 cases, high-dose cyclophosphamide (HD-CPA) for stem cell harvest after three or four cycles of VAD in 5 cases, high-dose melphalan followed by autologus stem-cell transplantation (HD-Mel+ASCT) in 6 cases, and administration of thalidomide at least for two months in 7 cases. First, total myeloma cells decreased after VAD, however, immature myeloma cells increased relatively (9/10). Second, HD-CPA was not effective in reducing myeloma cells furthermore after VAD (5/5). Third, HD-Mel+ ASCT could reduce immature myeloma cells clearly (4/6). In particular, a less than 5% reduction of immature myeloma cells after this course were important for the long duration of good response, but the residue of immature myeloma cells was a predictor of progressive disease (PD). Interestingly, MP was also useful to reduce immature myeloma cells (2/2). Finally, thalidomide was effective in reducing mature and intermediate myeloma cells (3/6), but not effective in immature myeloma cells. In conclusion, melphalan, if it is high-dose, has more effects on immature myeloma cells compared with those of other drugs, which might be a reason of the superiority of HD-Mel+ASCT over conventional treatment in terms of the response rate and event-free survival.

Comparison of Interferon Versus Thalidomide Versus RIC Allotransplant for Maintenance /Consolidation Therapy after Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: A Single Center Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1168-1168 ◽  
Author(s):  
Roland Fenk ◽  
Thorsten Graef ◽  
Ingmar Bruns ◽  
Leilani Ruf ◽  
Zohren Fabian ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose ◽  
Consolidation Therapy ◽  
Interferon Treatment ◽  
The Impact

Abstract High dose chemotherapy (HDT) with autologous stem cell transplantation has improved response rates and survival of patients with multiple myeloma. However the majority of patients suffer from relapse. Therefore, in this retrospective study we evaluated the impact of maintenance therapy with either thalidomide or interferon on the progression-free survival (PFS) after HDT and compared these results with a planned allogeneic transplant with reduced intensity conditioning (RIC) as consolidation therapy after HDT. We analysed 95 patients with a median age of 55 years who were treated at our institution in 2001–2005 with the diagnosis of stage III myeloma. Melphalan 200 mg/m2 was used as conditioning regimen followed by autologous stem cell transplantation. Interferon was given at a dose of 1.0 to 4.5 million U three times a week and the daily dose of thalidomide was 100 to 400 mg according to the individual tolerance of side effects. Allotransplants were performed with HLA-identical sibling donors after fludarabin 90 mg/m2 and TBI (2Gy) conditioning. In median 3.8 months after single HDT patients received either a RIC allotransplant (n=14) or maintenance therapy with thalidomide (n=39) or interferon (n=30) or no maintenance therapy (n=12). Prognostic factors such as cytogenetic abnormalities, beta-2 microglobulin, chemosensitive disease before HDT or remission status after HDT were equally distributed in all treatment groups. After a median follow-up of 33 months (range: 8–60) PFS from the start of treatment did not differ between patients after allotransplant (median not yet reached) and patients receiving thalidomide (median 50 months, p=0.8) but was significantly improved in comparison to patients who received interferon or no maintenance therapy (median 24 months, p&lt;0.0001). Most patients who received interferon or no maintenance therapy were treated with thalidomide at the time of relapse. Therefore, we also compared the combined PFS of patients treated with interferon maintenance followed by thalidomide in first relapse with the PFS of patients treated with immediate thalidomide maintenance therapy. Most interestingly, PFS of these two treatment schedules was not different (median 50 months in both groups; p=0.9), but the time of thalidomide exposure was in median 13 months shorter for patients in the interferon treatment arm. This is important, as to date most novel therapies hold the risk of polyneuropathy and thus pre-existing polyneuropathy due to prior thalidomide therapy limits the therapeutical options during the course of disease. Analysis of overall survival showed no differences between patients in the thalidomide or the interferon treatment arm (median not reached in both groups, p=0.5), but survival was inferior with RIC allotransplant (median 44 months, p=0.02). In conclusion, thalidomide is an effective maintenance therapy which prolongs PFS after single HDT. Interferon is less effective but the treatment schedule interferon maintenance therapy followed by thalidomide at the time of relapse is equal to upfront thalidomide maintenance therapy in terms of cumulative PFS and may be less toxic. RIC allotransplant is not superior to other treatment options and thus still has to be considered an experimental treatment option.

166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2684-2691 ◽  
Author(s):  
Sergio Giralt ◽  
William Bensinger ◽  
Mark Goodman ◽  
Donald Podoloff ◽  
Janet Eary ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase 1 ◽  
High Dose ◽  
Two Phase ◽  
Hematopoietic Stem

Abstract Holmium-166 1, 4, 7, 10-tetraazcyclododecane-1, 4, 7, 10-tetramethylenephosphonate (166Ho-DOTMP) is a radiotherapeutic that localizes specifically to the skeleton and can deliver high-dose radiation to the bone and bone marrow. In patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation two phase 1/2 dose-escalation studies of high-dose 166Ho-DOTMP plus melphalan were conducted. Patients received a 30 mCi (1.110 Gbq) tracer dose of 166Ho-DOTMP to assess skeletal uptake and to calculate a patient-specific therapeutic dose to deliver a nominal radiation dose of 20, 30, or 40 Gy to the bone marrow. A total of 83 patients received a therapeutic dose of 166Ho-DOTMP followed by autologous hematopoietic stem cell transplantation 6 to 10 days later. Of the patients, 81 had rapid and sustained hematologic recovery, and 2 died from infection before day 60. No grades 3 to 4 nonhematologic toxicities were reported within the first 60 days. There were 27 patients who experienced grades 2 to 3 hemorrhagic cystitis, only 1 of whom had received continuous bladder irrigation. There were 7 patients who experienced complications considered to be caused by severe thrombotic microangiopathy (TMA). No cases of severe TMA were reported in patients receiving in 166Ho-DOMTP doses lower than 30 Gy. Approximately 30% of patients experienced grades 2 to 4 renal toxicity, usually at doses targeting more than 40 Gy to the bone marrow. Complete remission was achieved in 29 (35%) of evaluable patients. With a minimum follow-up of 23 months, the median survival had not been reached and the median event-free survival was 22 months. 166Ho-DOTMP is a promising therapy for patients with multiple myeloma and merits further evaluation. (Blood. 2003;102:2684-2691)

Immune control of cytomegalovirus reactivation in stem cell transplantation

Blood ◽  
2021 ◽  
Author(s):  
Mariapia A Degli-Esposti ◽  
Geoffrey R Hill
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Antiviral Immunity ◽  
Antiviral Drugs ◽  
Viral Reactivation ◽  
High Dose ◽  
Cytomegalovirus Reactivation ◽  
The Impact

The reactivation of viruses from latency after allogeneic stem cell transplantation (SCT) continues to represent a major clinical challenge requiring sophisticated monitoring strategies in the context of prophylactic and/or pre-emptive antiviral drugs that are associated with significant expense, toxicity, and rates of failure. Accumulating evidence has demonstrated the association of polyfunctional virus-specific T-cells with protection from viral reactivation, affirmed by the ability of adoptively transferred virus-specific T-cells to prevent and treat reactivation and disease. The roles of innate cells (NK cells) in early viral surveillance, and dendritic cells in priming of T-cells have also been delineated. Most recently, a role for strain-specific humoral responses in preventing early cytomegalovirus (CMV) reactivation has been demonstrated in preclinical models. Despite these advances, many unknowns remain: what are the critical innate and adaptive responses over time, is the origin (e.g. recipient versus donor) and localization (e.g. in parenchymal tissue versus lymphoid organs) of these responses important, how does GVHD and the prevention/treatment thereof (e.g. high dose steroids) impact the functionality and relevance of a particular immune axis, do the immune parameters that control latency, reactivation and dissemination differ, and what is the impact of new antiviral drugs on the development of enduring antiviral immunity. Thus, whilst antiviral drugs have provided major improvements over the last two decades, understanding the immunological paradigms underpinning protective antiviral immunity after SCT offers the potential to generate non-toxic immune-based therapeutic approaches for lasting protection from viral reactivation.

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