Role of Serum Lactate Dehydrogenase (LDH) As a Prognostic Marker for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3115-3115
Author(s):  
Krina Patel ◽  
Robert Z. Orlowski ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Lactate Dehydrogenase ◽  
Hematopoietic Stem Cell Transplantation ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Abstract 3115 Background: The International Staging System (ISS), chromosomal abnormalities, and response to therapy are well recognized predictors of outcome in multiple myeloma (MM). However, the role of serum lactate dehydrogenase (LDH) as a prognostic marker for MM is not well established. Recently we showed that high LDH at diagnosis of MM is a predictor of shorter survival. Here we report the impact of the LDH level at the time of autologous hematopoietic stem cell transplantation (auto-HCT) on its outcome. Methods: We evaluated 1,658 patients with symptomatic myeloma who underwent auto-HCT from July 1988 to December 2010 at our institution. The primary objective was to determine the impact of high LDH (>1000 IU/L) level, obtained on the start day of the preparative regimen, on progression free survival (PFS) and overall survival (OS). Results: Patient characteristics according to LDH level at auto-HCT are summarized in Table 1. Patients in the 2 LDH groups (>1000 or ≤ 1000) were matched for age, gender, disease status, and response to prior therapy at the time of auto-HCT. Patients with LDH >1000 IU/L had a significantly higher beta-2 microglobulin (β2m) and bone marrow plasmacytosis at the time of auto-HCT. Median times to neutrophil (10 vs. 10 days: p=0.10) and platelet engraftment (11.3 vs.12.2 days: p=0.20) were not different in the 2 groups. Also, there was no significant difference in CR, VGPR, PR or overall response rates between the 2 groups. Median follow up was 35 months (1 to 244). Median OS in patients with LDH >1000 and ≤ 1000 were 49.2 and 68.0 months, respectively (p=0.03). Median PFS in patients with LDH >1000 and ≤ 1000 were 14.4 and 24.7 months, respectively (p=0.001). On univariate analyses, >10% plasma cells in bone marrow biopsy, relapsed disease, serum β2M ≥ 3.5 at auto-HCT, presence of any chromosomal abnormality, and < PR after auto-HCT were associated with significantly shorter PFS and OS. Conclusions: Having a serum LDH value of >1000 IU/L prior to auto-HCT is associated with shorter PFS and OS in patients with MM. These high risk patients may require aggressive post-transplant therapy, including consolidation, maintenance, tandem transplants or novel approaches like immunotherapy. Disclosures: Shah: Celgene: Membership on an entity's Board of Directors or advisory committees.

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)

Prognostic value of serum lactate dehydrogenase in symptomatic multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8093-8093 ◽  
Author(s):  
Krina K. Patel ◽  
Robert Z. Orlowski ◽  
Donna M. Weber ◽  
Michael Wang ◽  
Sheeba K. Thomas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Lactate Dehydrogenase ◽  
Prognostic Value ◽  
Intensive Therapy ◽  
Serum Lactate ◽  
Response To Therapy ◽  
Stage Iii ◽  
Serum Lactate Dehydrogenase ◽  
Survival Times ◽  
The Impact

8093 Background: In patients with symptomatic multiple myeloma, the clinical features, responses to treatment, and survival times vary. Well established predictors of survival include the International Staging System (ISS), cytogenetic abnormalities, and response to therapy. Long recognized has been the association of high serum lactate dehydrogenase (LDH) with advanced disease and shorter survival. We focused here on the impact of high LDH on staging and prognosis in order to guide the role of recent advances in therapy. Methods: We evaluated 1,247 patients with newly diagnosed, symptomatic myeloma from 10/74 to 7/11. Our goal was to determine the prognostic value of high LDH (>300 IU/L) in relation to ISS stage. We also compared the frequencies of anemia, hypercalcemia, and response to therapy in patients with high LDH with those of patients with Stage III disease and normal LDH values. Results: All 1,139 patients with normal LDH lived significantly longer than the 108 patients with elevated values (47 vs. 16 months, p <.01). LDH was elevated in 9% of all patients, but in 2%, 6%, and 18% of patients with ISS-I, II, and III disease, respectively. Their survival times were also significantly shorter than those of comparable patients in each stage with normal LDH (table). Among the 108 patients with high LDH, the frequencies of hemoglobin <8.5 g/dl (54 vs. 41%, p=.03), and serum calcium>11.5 mg/dl (41 vs. 27%, p<.01) were significantly higher than those of 292 patients with Stage III disease and normal LDH, and the frequency of response to therapy was less (40 vs. 62%, p<.01). Conclusions: Serum lactate dehydrogenase provides a convenient and dependable prognostic indicator in patients with multiple myeloma. An elevated LDH value indicates a poor prognosis regardless of ISS stage, confirming the report by Gkotzamanidou, Terpos, and Dimopoulos et al, and should be included in the definition of stage III disease. Such patients require rapid control of disease with sequential combinations of effective drugs and intensive therapy in order to improve their outcome. [Table: see text]

scholarly journals Durable Remission and Survival in Relapsed/Refractory Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5884-5884 ◽  
Author(s):  
A. Megan Cornelison ◽  
Rima M Saliba ◽  
Sairah Ahmed ◽  
Yago Nieto ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Durable Remission

Abstract Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the setting of refractory multiple myeloma (MM) is still controversial. Although potentially curative in a subset of pts, concerns regarding treatment related mortality (TRM) and graft vs. host disease (GVHD) preclude its universal use. In this study, we evaluated the role of allo-HSCT for pts with relapsed MM. Methods: 110 consecutive pts with relapsed MM underwent allo-HSCT at our institution between 2000 and 2014. The primary objective was to assess progression-free (PFS) and overall survival (OS). Results: Median age at allo-HSCT was 54 (range, 32-71) years and median time from diagnosis to allo-HSCT was 35.7 (range, 8.6 to 228.8) months. Fifty-two (47%) and 49 (45%) pts had standard-risk (SR) and high-risk (HR) cytogenetics at the time of allo-HSCT, respectively. Pts received a median of 5 (range, 1-9) prior chemotherapy regimens and 99 (90%) pts had at least 1 (range, 0-3) prior auto-HSCTs. One hundred one (92%) pts received either a proteasome inhibitor (PI) or an immunomodulatory drug (IMiD) prior to allo-HSCT, with 65 (59%) receiving both. Sixty eight (62%) received allo-HSCT from matched related, 34 (31%) from matched unrelated, 5 (4%) from cord blood, and 3 (3%) from mismatched donors. Preparative regimen was fludarabine/melphalan-based in 88 (80%) and fludarabine/busulfan-based in 16 (15%) pts. Median time to neutrophil and platelet engraftment was 12 (range, 8-30) and 13 (range, 0-81) days, respectively. Ten pts died of non-relapse causes within 100 days (100-day TRM: 9%) and 21 (19%) within 1 year. Grade 1-4 acute GVHD was seen in 50 (45%) and cGVHD in 35 (32%) pts, respectively. Eighteen (16%) achieved a CR, 26 (23%) a VGPR and 38 (34%) achieved a PR, with an overall response rate of 73%. With a median follow up of 41.9 months (range, 6.4 to 172.9) in surviving pts, 1- and 2-year PFS were 23% and 15%, respectively (Fig 1). One and 2-year OS were 50% and 32%, respectively (Fig 2). HR cytogenetics at allo-HSCT were associated with a significantly shorter 2-year PFS (6% for HR vs. 23% for SR; p=0.007) and OS (p=0.01). A response <PR after allo-HSCT was also associated with significantly shorter 2-year PFS (p<0.001) and OS (p<0.001). Conclusions: Allo-HSCT is associated with durable remission and survival in approximately 15% of heavily pretreated pts with relapsed/refractory MM. Novel, more effective approaches are needed for patients with HR cytogenetic abnormalities. Figure 1 Progression-Free Survival Figure 1. Progression-Free Survival Figure 2 Overall Survival Figure 2. Overall Survival Disclosures No relevant conflicts of interest to declare.

Prolonged Thrombocytopenia Is Associated With Increases Of CD8+ CX3CR1+ Cells In The Bone Marrow After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5494-5494
Author(s):  
Xiaohui Zhang ◽  
Guoxiang Wang ◽  
Honghu Zhu ◽  
Yanrong Liu ◽  
Daihong Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cd8 T Cells ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Prolonged thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT),which is associated with a high mortality and poor prognosis. The aim of this study was to assess the impact of the CD8+CX3CR1+ T cells on the development and maturation of megakaryocytes in patients with the prolonged thrombocytopenia after allo-HSCT in order to identify the risk factors related to thrombocytopenia after allo-HSCT. The changes in CD8+ T cells and their homing receptors CX3CR1, CXCR4 and VLA-4 in bone marrow of patients( N=89) with and without (N=94 ) prolonged thrombocytopenia following allo-HSCT and the impact of activated CD8+ T cells on apoptosis and ploidy of megakaryocytes in vitro ware determined. The percentage of CD8+CX3CR1+ T cells was significantly higher in prolonged thrombocytopenia patients than control (P<0.001).The increase in CD8+ T cells was not observed in peripheral blood. Patients with prolonged thrombocytopenia exhibited a marked increase in the number of low ploidy(≤8) megakaryocytes compared to those without(P<0.05). Depletion of CD8+ T cells increased apoptosis of megakaryocytes (P<0.05), which was corrected by reconstitution of CD8+ T cells (P<0.05). We demonstrated that prolonged thrombocytopenia is associated with increased expression of CX3CR1 and recruitment of CD8+ T cells into the bone marrow. Activated CD8+ T cells suppress apoptosis of megakaryocytes in vitro. Our findings shed light on the prolonged thrombocytopenia is associated with increases of CD8+ CX3CR1+ cells in the bone marrow after allo-HSCT patients. Disclosures: No relevant conflicts of interest to declare.

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