scholarly journals Symptomatic Outcome of CTDa In Multiple Myeloma Patients

KYAMC Journal ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 124-128
Author(s):  
Zulfia Zinat Chowdhury ◽  
Mohammad Ali ◽  
AKM Mynul Islam ◽  
Salina Haque ◽  
Tamanna Bahar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Cost Effective ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Albumin Level ◽  
High Dose ◽  
Female Ratio ◽  
Stem Cell Rescue ◽  
Bone Marrow Plasma

Background: Multiple Myeloma (MM) represents approximately 15% of all hematological malignancies. Despite the use of high-dose chemotherapy followed by stem cell rescue MM remains incurable at present. The goal is to control the disease as much as possible, providing the best quality of life to patients for the longest duration. Currently, CTDa (attenuated Cyclophosphamide, Thalidomide, Dexamethasone) is the best option of treatment as it is cost-effective, with no need for hospitalization with a good response. Objective: To find out the symptomatic responses and toxicities of CTDa in Multiple Myeloma patients. Materials and Methods: 25 patients of newly diagnosed MM patients were treated in the Haematology Department, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2016 to July 2017. The mean age of the patients was 54 years, Male female ratio was 1.5:1 and most of the patients were farmers. After induction of 4 to 6 cycles of CTDa all patients were followed up at 6th and 12th weeks. At follow up we evaluated improvement of weakness, bone pain, Hb%, ESR, monoclonal protein, ß2microglobulin, bone marrow plasma cells and serum calcium and albumin level. Adverse effects, such as peripheral neuropathy, thromboembolic events, hyperglycemia, constipation, rash, and somnolence were also assessed. Results: Among 25 patients, complete response achieved only 13 patients (52%), where 20% and 16% of patients belonged to partial or no response respectively. The death occurred in 2 cases (12%). Conclusion: CTDa is a gentle approach to treat an especially frail group of patients, since virtually all patients ultimately relapse. KYAMC Journal Vol. 11, No.-3, October 2020, Page 124-128

PTEN Gene Deletions in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4889-4889
Author(s):  
Xiao Ying Qi ◽  
A. Keith Stewart ◽  
Hong Chang
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Myeloma Cell ◽  
Suppressor Gene ◽  
High Dose Chemotherapy ◽  
Pten Gene ◽  
Allelic Loss ◽  
High Dose ◽  
13Q Deletion

Abstract PTEN, a tumor suppressor gene, negatively regulates the anti-apoptotic action of akt phosphorylation. Allelic loss or mutation of this gene has been detected in many solid tumors and more recently in human myeloma cell lines (HMCLs). Expression of PTEN has resulted in growth inhibition and apoptosis of a HMCL, suggesting that it may play a role in the pathogenesis of multiple myeloma (MM). However, the PTEN status in tumor cells from patients with MM has not been determined. Using a triple staining method combining staining for cytoplasmic light chains and fluorescence in situ hybridization (FISH) with chromosome 10-centromere and PTEN-gene specific probes, we analyzed clonal plasma cells from 71 patients with MM, 10 with plasma cell leukemia (PCL) and 10 HMCLs. Hemizygous PTEN deletions were detected in 4 of 71 (5.6%) MM patients, 2 of 10 (20%) PCLs, and 2 of 10 (20%) HMCLs. The percentages of clonal plasma cells containing PTEN deletions ranged from 21–90% (median, 56%). Three of the 4 patients with PTEN deletions were detected at diagnosis with stage III disease (Duire-Salmon) and 1 was detected at relapse. Two patients had IgG kappa, 1 IgG lambda and 1 free lambda light chain. To correlate the PTEN status with other known genetic abnormalities in MM, we investigated 4 MM and 2 PCLs with PTEN deletions using FISH for chromosome13q, p53 status, translocations t(11;14), t(4;14) and t(14;16). One MM had a 13q deletion, 1 PCL had a t(11;14), and the other PCL had a t(14;16), a 13q deletion and a p53 deletion. All 4 MM patients with hemizygous PTEN deletions received melphalan based high-dose chemotherapy and autologous stem cell support. Their median overall survival (OS) was 48.1months, and progression free survival (PFS) was 42.8 months as compared to patients without PTEN deletions (OS, not reached, PFS, 25.8 months) (p=0.51 for OS, p=0.67 for PFS). Our results indicate that PTEN deletions are uncommon in MM patients and therefore unlikely represent a primary event for MM. PTEN deletions appear to occur in the advance stage of the disease, and are more frequently involved in PCL or HMCLs suggesting that deletions of PTEN may be associated with disease progression in a subset of MM.

Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4210-4210
Author(s):  
Luiza soares Vieira ◽  
Edvan de queiroz Crusoe ◽  
Manuella de S. Sampaio Almeida ◽  
Lais Sousa ◽  
ana Lucia Perez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Oligoclonal Bands ◽  
High Dose ◽  
Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparison of Two Post-Transplant Predictive Indexes: Day 100 is a Better Time-Point for Response Evaluation after Autologous Stem Cell Transplantation in Multiple Myeloma: Ass Retrospective Study

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Ma’koseh M ◽  
◽  
Sa’deh S ◽  
Halahleh K ◽  
Abu-Jazar H ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Response Evaluation ◽  
Therapeutic Implications ◽  
Significant Difference

In Multiple Myeloma (MM), response to High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT) has important prognostic and therapeutic implications. Best timing for response evaluation after ASCT is not well studied. Our study evaluated the correlation between response on day 30 and day 100 after ASCT with Progression Free Survival (PFS) and Overall Survival (OS) in 119 MM patients. Median follow-up was 39.8 months. Complete Response (CR) was achieved in 53.8% and 55.5% of patients on D 30 and D 100, respectively. On D30, there was no significant difference in PFS or OS in CR vs. no CR group (35.4 vs. 22.1 months, p: 0.058) and (92.6 months vs. not reached p: 0.96) respectively nor in responders (R) vs. Non-Responders (NR) group (97.8 vs. 47.1 months p: 0.08) and (30.2 vs. 18.9 months, p: 0.09) respectively. While on D100, PFS was significantly better in CR vs. no CR group (33.8 vs. 18.1 months, p: 0.0047) as well as in R vs. NR (30.6 vs. 16.9 months p: 0.015). However, OS was not better in either (92.6 vs. 52.1 months p: 0.46) and (92.6 months vs. not reached p: 0, 88) respectively. In conclusion, after HDC and ASCT for MM, we recommend doing response evaluation on D100 rather than D30 as it better correlates with PFS. Further studies are required to confirm this finding in the era of consolidation and maintenance treatment.

Utilization and outcomes of high-dose chemotherapy and stem-cell rescue in patient with testicular cancer from 2005 to 2014 in United States.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18246-e18246
Author(s):  
Aakash Desai ◽  
Devashish Desai ◽  
Pushti Khandwala ◽  
Smith Giri ◽  
Leonard Joseph Appleman ◽  
...  
Keyword(s):  
United States ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Testicular Cancer ◽  
High Dose Chemotherapy ◽  
Matched Pair ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Stem Cell Rescue ◽  
Matched Pair Analysis

e18246 Background: Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue. This regimen is commonly used as salvage therapy, third-line or later therapy in patients with platinum-refractory disease. The utilization and real-world outcomes and complications of patients with testicular cancer undergoing autologous hematopoietic stem cell transplant (aHSCT) in United States are unknown. Methods: We queried National Inpatient Sample, a large inpatient data set in the United States, from 2005 to 2014 for male patients with testicular cancer or multiple myeloma (control group) receiving aHSCT and compared outcomes between these groups. The primary outcome was in-hospital mortality rate, and the secondary outcomes included in-hospital complications of aHSCT, length of stay and total charges. Outcomes were assessed by means of univariate analysis, multivariate regression and propensity score matched-pair analysis. Results: A total of 391 patients (weighted N = 1,909) with testicular cancer and 4,809 male patients (weighted N = 23,501) with multiple myeloma who underwent aHSCT from 2005 to 2014 were identified. Mean age of patients with testicular cancer was 32.3 years vs 59 years for multiple myeloma patients (p < 0.001) There were no differences in in-hospital mortality rates (1.5% vs 1.4%, p = 0.85) or rates of intubation (2.3% vs 1.6%, p = 0.36), sepsis (7.7% vs 7.5%, p = 0.94), bacteremia (13.5% vs 15.6%, p = 0.42), or stomatitis (43.8% vs 38.8%, p = 0.87) between patients with testicular cancer and multiple myeloma receiving autologous HSCT. However, utilization of total parenteral nutrition was higher in patients with testicular cancer (12.9% vs 4.7%, p < 0.001). There was no difference in length of stay (17.5 vs 17.5 days, p = 0.77) and total charges (121,120$ vs 123,729$, p = 0.74) between two groups. The results were consistent in multivariate and propensity score matched-pair analysis. Conclusions: The in-hospital outcomes of patients with testicular cancer receiving aHSCT appears to be similar to patients with multiple myeloma. However, overall utilization of aHSCT for testicular cancer appears to be low in United States.

NCOG-36. LONG-TERM SURVIVAL AND COGNITIVE FUNCTION FOLLOW UP OF PRIMARY CNS LYMPHOMA TREATED WITH R-MVP FOLLOWED BY HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANT CONSOLIDATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi160
Author(s):  
Kate Therkelsen ◽  
Christian Grommes
Keyword(s):  
Stem Cell ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Consolidation Therapy ◽  
Term Survival ◽  
Stem Cell Rescue ◽  
Long Term Follow Up

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare central nervous system malignancy, and long-term follow up studies are uncommon. First line therapy is based on high-dose methotrexate and different consolidation therapy options. This is a long-term follow up study of PCNSL patients enrolled in a prospective trial using R-MPV chemotherapy regimen followed by high dose chemotherapy and autologous stem cell rescue to determine long-term survival and cognitive effects. METHODS From June 2005 to September 2011, 32 newly diagnosed immunocompentent PCNSL were enrolled. Patients received 5-7 doses of rituximab (500mg/m2), methotrexate (3.5 gm/m2), procarbazine (100mg/m2), and vincristine (1.4mg/m2) (R-MVP). Consolidation therapy consisted of high dose chemotherapy (HDC) with thiotepa (250 mg/m2), busulfan (3.2 mg/kg), and cyclophosphamide (60 mg/kg), followed by autologous stem cell rescue (ASCT) in those with partial or complete response to R-MVP. Long-term follow-up status including disease status, cognitive status (KPS, NANO score), and leukoencephalopathy (modified Fazkas Scale) were collected. RESULTS 26 of 36 underwent HDC and ACST. Of those, 3 died due to treatment related effects; 2 died of disease progression within two years after ASCT. After a median follow-up of 10.5 years, none of the remaining 21 patients progressed. At the time of last follow up, the median KPS was 90, compared to 80 at time of ASCT. The median NANO score and leukoencephalopathy score post ASCT and at follow-up did not change. Of note, 2 of 4 patients with a partial or complete response to R-MVP that elected not to proceed with HDC-ASCT consolidation, experienced progression at a mean of 52 months. CONCLUSION Long-term follow up demonstrates that treatment was tolerated well with stable leukoencephalopathy on MRI and good performance status. Disease recurrence 2 years after HDC with ASCT consolidation was not observed.

Decreased Thymosin Beta 4 Expression Results in Poor Prognosis and Decreased Survival in Multiple Myeloma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1703-1703
Author(s):  
Jo Caers ◽  
Dirk Hose ◽  
Ine Kuipers ◽  
Tomas Jan Bos ◽  
Els Van Valckenborgh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Metastatic Potential ◽  
Suppressor Gene ◽  
Inhibitory Effect ◽  
High Dose Chemotherapy ◽  
Tumor Formation ◽  
High Dose ◽  
Thymosin Beta 4 ◽  
Qrt Pcr

Abstract Thymosin beta 4 (Tβ4) is a small cytoplasmic and nuclear protein involved in different cellular processes including differentiation, migration and proliferation. It is overexpressed in several malignant cells, resulting in an increased angiogenic respons and metastatic potential of tumor cells. In the current study we wanted to evaluate the expression of Tβ4 in primary human multiple myeloma cells (MM) and murine 5TMM cells. Microarray analysis and qRT-PCR of 171 MM patients treated with high dose therapy and autologous stem cell transplantation, showed that MM cells display a decreased Tβ4 expression compared to plasma cells from healthy individuals. We investigated whether Tβ4 expression in MM cells influences the event free (EFS) and overall survival (OAS) of these patients. As Tβ4 was expressed in all MM cells, we compared survival of patients with Tβ4 expression in MM cells in the upper thirtile (Tβ4high MMC) against the lowest thirtile (Tβ4low MMC). Patients with Tβ4high MMC had an increased EFS (P&lt; 0.05) and also their OAS tended to be longer. A similar observation was made in the 5TMM model where qRT-PCR and ELISA revealed a decreased expression of Tβ4 in BM samples from 5T33MM and 5T2MM diseased mice compared to control mice. To study the functionality of Tβ4, we overexpressed Tβ4 in 5T33MMvitro (5T33MMvt) cells by lentiviral transduction. These 5T33MMvt-Tβ4+ cells demonstrated a significantly decreased proliferative capacitity and an increased sensitivity to different anti-myeloma agents (bortezomib, melphalan, dexamethasone) compared to control 5T33MMvt cells. Furthermore, injection of 5T33MMvt-Tβ4+ cells in C57BlKaLwRij mice resulted in a significant decreased tumor formation (paraprotein concentration was 1.92 g/dl versus 3.74 g/dl for untransduced cells, p&lt;0.05) and a prolonged survival compared to mice injected with untransduced 5T33MMvt cells (respectively 65.9 days versus 88.9 days, p&lt; 0.05). In conclusion, we found a decreased Tβ4 expression in human and murine MM cells compared to normal plasma cells. In our cohort of MM patients treated with high-dose chemotherapy, low expression of TB4 identifies a group of patients with adverse prognosis while in the murine 5TMM33vt model, overexpression of Tβ4 resulted in an inhibitory effect on tumor formation suggesting a role of Tβ4 as a tumor suppressor gene in MM.

scholarly journals MBCL-29. PHASE I/II STUDY OF SEQUENTIAL HIGH-DOSE CHEMOTHERAPY WITH STEM CELL SUPPORT IN CHILDREN YOUNGER THAN 5 YEARS OF AGE WITH HIGH-RISK MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii394-iii395
Author(s):  
Christelle Dufour ◽  
Julien Masliah-Planchon ◽  
Marie-Bernadette Delisle ◽  
Anne Geoffray ◽  
Rachid Abbas ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Phase I ◽  
Complete Response ◽  
Multicenter Trial ◽  
High Dose Chemotherapy ◽  
Craniospinal Irradiation ◽  
High Dose ◽  
Stem Cell Rescue

Abstract PURPOSE To assess the 3-year EFS rate of children younger than 5 years of age with high-risk medulloblastoma (MB) treated according to the prospective multicenter trial HR MB-5. PATIENTS AND METHODS After surgery, all children received 2 cycles of Etoposide- Carboplatine. If partial (PR) or complete response (CR) was achieved after induction chemotherapy, children received 2 courses of thiotepa (600mg/m²) with stem cell rescue. For patients in CR after high-dose chemotherapy, they received one course of Cyclophosphamide – Busilvex with stem cell rescue (Phase I part). The others patients (not in PR after induction or in CR after thiotepa) were treated with 2 cycles of Temozolomide-Irinotecan followed by age-adapted craniospinal irradiation and maintenance treatment. RESULTS 28 children (2 to 4 years; median: 3.0 years) were enrolled. Group 3 MB were most common (57%). The response rate to Etoposide-Carboplatine was 60.7%. Among 20 patients treated with Thiotepa, 13 children were in CR and received Cyclophosphamide – Busilvex without radiotherapy. Out of them, 9 patients (45%) are alive in CR without craniospinal irradiation (median follow-up 5 years). Among 15 patients treated with radiotherapy, 8 patients are alive (median follow-up 3.8 years). The study was prematurely stopped for an excess of events. The median follow-up was 4 years (range 1.5 - 6.1). The 3-year EFS and OS were 42.3% [25.9 - 60.6] and 71.3% [52.7 - 84.7], respectively. CONCLUSIONS This risk-adapted strategy did not improve EFS in young children with high-risk MB. However, the study shows that good responders to chemotherapy can be cured without recourse to irradiation.

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