Peripheral Blood Progenitor Cell Transplantation in Multiple Myeloma Following High-Dose Melphalan-Based Therapy

Goldschmidt, Hartmut; Hegenbart, Ute; Wallmeier, M.; Hohaus, Stefan; Engenhart, R.; Wannenmacher, M; Haas, Rainer

doi:10.1007/978-3-642-46836-0_4

Cited by 16 publications

(6 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Median mobilization days, CD34 þ cells/kg and total leukaphereses were 16 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), 12.1 million (2.6-52.8), and 2 (1)(2)(3)(4)(5) respectively.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Autologous hematopoietic cell transplantation (HCT) is standard therapy especially in younger patients. [3][4][5] A recent phase III trial showed a survival advantage of 10 months in patients who underwent HCT, with a trend toward improved survival in patients with high-risk disease (b 2 microglobulin 48.0 mg/l). 6 All patients eventually relapse and sources of relapse include minimal residual disease post-HCT and possibly infusion of contaminating myeloma cells at the time of stem cell infusion.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial

Gupta

Zhou

Hassoun

et al. 2005

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Multiple myeloma (MM) is an incurable hematologic malignancy for which autologous hematopoietic stem cell transplantation (HCT) is a standard therapy. The optimal method of stem cell mobilization is not defined. We evaluated intravenous melphalan (60 mg/m 2 ), the most effective agent for MM, and G-CSF (10 lg/kg/day) for mobilization. End points were safety, adequacy of CD34 þ collections, MM response, and contamination of stem cell components (SCC). In total, 32 patients were mobilized. There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3-17). Median mobilization days, CD34 þ cells/kg and total leukaphereses were 16 (12-30), 12.1 million (2.6-52.8), and 2 (1-5) respectively. Four patients (12.5 %) failed to achieve the target of 4 million CD34 þ cells/kg in five leukaphereses. Reduction in myeloma was seen in 11 patients (34%) with 3 (9%) achieving complete response; 15 (47%) maintained prior responses. Estimated MM contamination per SCC (N ¼ 48) was 0.0009% (range 0-0.1) and 0.21 Â 10 4 cells per kg (range 0-41.2). Increased contamination was associated with increased patient age. This strategy for mobilization is feasible, frequently requires hospitalization and transfusion, and controls disease in most patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial

Gupta

Zhou

Hassoun

et al. 2005

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…[4][5][6][7][8][9][10][11] Similarly, a case-control study showed excessive morbidity and no added benefit with the addition of total body irradiation. 12 The IFM as a study is currently addressing this issue in a randomized trial. TBI is also associated with significant morbidity, particularly in older individuals, as evidenced by 8% early deaths in patients receiving TBI in this study.…”

Section: Discussionmentioning

confidence: 99%

Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone

Desikan

Tricot

Dhodapkar

et al. 2000

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m 2 . Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m 2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m 2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatmentrelated mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P Ͻ 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. with tandem autotransplants in previously untreated patients. In a pair-mate analysis, this approach (termed 'Total Therapy') led to a significantly higher CR, overall survival (OS) and event-free survival (EFS), when compared to a matched cohort of patients treated with conventional-dose therapy on Southwest Oncology Group trials. 2 In these initial studies, patients who failed to achieve a partial remission (PR) after the first transplant (Tx-1), received high-dose melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen for the second autotransplant (Tx-2). Even in this primary unresponsive group of patients, a second high-dose cycle induced a CR in 10% and PR in 55%. Among patients achieving уPR after Tx-1, Tx-2 utilizing MEL-200 led to attainment of CR in 38%, resulting in an increase in the cumulative CR rate on an intent-totreat basis from 24 to 43%. With the hypothesis that the benefit of more dose-intense conditioning with MEL-TBI or MEL-CY may be even more effective in the patients responding to Tx-1, we applied these regimens to 43 patients achieving уPR after Tx-1. In this study, we have compared the outcome of patients attaining уPR after Tx-1 and receiving MEL 200 + cyclophosphamide for Tx-2 (group 1) or Mel 140 + TBI (group 2) with a matched group of patients receiving MEL 200 as conditioning for Tx-2 (group 3). Each group was evaluated for treatment response, survival, engraftment kinetics and toxicities. Patients and methodsForty-three myeloma patients achieving at least a PR after Tx-1 with MEL 20...

show abstract

“…In both the cases, antibiotics are given to combat infection and the bone marrow is replenished by transplanting bone marrow or hematopoietic stem cells (Madonna et al, 1991). However, to decrease the circulating mononuclear cells or decrease the availability of BMDCs, a sub lethal whole body irradiation or lower dose of chemotherapeutics can be used (Andrade et al, 2011; Garg et al, 2010; Goldschmidt et al, 1998; Kallmeyer et al, 1998; Ma et al, 2003). There has not been any report showing that the relation of lower number of available BMDCs and the effect of vatalanib in GBM.…”

Section: Introductionmentioning

confidence: 99%

Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma

Shaaban

Alsulami

Arbab

et al. 2016

International J. of Cancer Research

View full text Add to dashboard Cite

Antiangiogenic agents caused paradoxical increase in pro-growth and pro-angiogenic factors and caused tumor growth in glioblastoma (GBM). It is hypothesized that paradoxical increase in pro-angiogenic factors would mobilize Bone Marrow Derived Cells (BMDCs) to the treated tumor and cause refractory tumor growth. The purposes of the studies were to determine whether whole body irradiation (WBIR) or a CXCR4 antagonist (AMD3100) will potentiate the effect of vatalanib (a VEGFR2 tyrosine kinase inhibitor) and prevent the refractory growth of GBM. Human GBM were grown orthotopically in three groups of rats (control, pretreated with WBIR and AMD3100) and randomly selected for vehicle or vatalanib treatments for 2 weeks. Then all animals underwent Magnetic Resonance Imaging (MRI) followed by euthanasia and histochemical analysis. Tumor volume and different vascular parameters (plasma volume (vp), forward transfer constant (Ktrans), back flow constant (kep), extravascular extracellular space volume (ve) were determined from MRI. In control group, vatalanib treatment increased the tumor growth significantly compared to that of vehicle treatment but by preventing the mobilization of BMDCs and interaction of CXCR4-SDF-1 using WBIR and ADM3100, respectively, paradoxical growth of tumor was controlled. Pretreatment with WBIR or AMD3100 also decreased tumor cell migration, despite the fact that ADM3100 increased the accumulation of M1 and M2 macrophages in the tumors. Vatalanib also increased Ktrans and ve in control animals but both of the vascular parameters were decreased when the animals were pretreated with WBIR and AMD3100. In conclusion, depleting bone marrow cells or CXCR4 interaction can potentiate the effect of vatalanib.

show abstract

Peripheral Blood Progenitor Cell Transplantation in Multiple Myeloma Following High-Dose Melphalan-Based Therapy

Cited by 16 publications

References 9 publications

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial

Melphalan plus total body irradiation (MEL-TBI) or cyclophosphamide (MEL-CY) as a conditioning regimen with second autotransplant in responding patients with myeloma is inferior compared to historical controls receiving tandem transplants with melphalan alone

Targeting Bone Marrow to Potentiate the Anti-Tumor Effect of Tyrosine Kinase Inhibitor in Preclinical Rat Model of Human Glioblastoma

Contact Info

Product

Resources

About