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Radiation Therapy Can Be Safely Incorporated into Pretransplantation Treatment Regimens for Patients with Multiple Myeloma
Damron, E. P., Qazilbash, M. H., Fang, P. Q., Wu, S. Y., Dabaja, B. S., Rondon, G., Hosing, C., Champlin, R. E., Bashir, Q., Shpall, E. J., et al
Transplantation and cellular therapy. 2023;29(1):37.e1-37.e7
Abstract
Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplantation (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. In this study, we retrospectively examined the possible effect of RT on PBPC collection. We reviewed the charts of 732 patients with MM treated with RT at our institution from 1999 to 2017, including patients who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage of bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlation and the t-test. The 732 MM patients included 485 planned for ASCT; of these, 223 received RT prior to PBPC collection and were included in the final cohort. The median age at PBPC collection was 59 years (range, 33 to 80 years). For SIT, patients received combination regimens including the following agents: bortezomib (142 patients; 64%), lenalidomide (111 patients; 50%), and alkylators (46 patients; 21%). Nine patients (4%) received dexamethasone alone. The median cumulative %BM treated per patient was 6.7 (range .0 to 47.4). The median RT dose was 24 Gy (range, 10.0 to 75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 patients; 85%), G-CSF with plerixafor (15 patients; 7%), or chemotherapy (19 patients; 9%). A median of 7.8 × 10(6) CD34(+)/kg PBPCs (range, .5 to 54.8× 10(6) CD34(+)/kg) were collected in a median of 3 (range, 1 to 9) apheresis procedures. One hundred ninety-six patients (99%) collected ≥2.0 × 10(6) CD34(+)/kg PBPCs, and 166 (83%) collected >5.0 × 10(6) CD34(+)/kg PBPCs. The number of PBPCs collected was not associated with %BM treated (P = .15) or RT dose (P = .56). The number of apheresis procedures performed was not associated with %BM treated (P = .54) or RT dose (P = .85). The amount of PBPCs collected did not differ significantly between patients receiving RT to the pelvis/sacrum (P = .20) and those receiving RT to the spine (P = .13). The time to platelet engraftment was longer for patients with higher %BM treated (P = .02). Eleven patients did not undergo a confirmed ASCT, owing to patient preference (3 patients), trial therapy (1 patient), comorbidities (1 patient), election for hospice (1 patient), inadequate collection (4 patients), or inadequate follow-up (1 patient). In our study cohort, RT prior to ASCT did not impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.
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Black multiple myeloma patients undergoing upfront autologous stem cell transplant have similar survival outcomes compared to whites: a propensity-score matched analysis
Patel, R., Ma, J., Bashir, Q., Delgado, R., Rondon, G., Popat, U. R., Hosing, C. M., Nieto, Y., Kebriaei, P., Alousi, A. M., et al
American journal of hematology. 2021
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Radiation Therapy can be Safely Incorporated Into Pre-Transplant Treatment Regimens for Patients With Multiple Myeloma
Damron, E. P., Qazilbash, M., Fang, P., Wu, S. Y., Dabaja, B., Rondon, G., Hosing, C., Champlin, R., Bashir, Q., Shpall, E. J., et al
International journal of radiation oncology, biology, physics. 2021;111(3s):S81
Abstract
PURPOSE/OBJECTIVE(S): Primary treatment of multiple myeloma (MM) often involves systemic induction therapy (SIT) followed by autologous stem cell transplant (ASCT). Radiation therapy (RT) is sometimes used for palliation; however, many practitioners avoid RT out of concern that future peripheral blood progenitor cell (PBPC) collection required for ASCT may be compromised. We retrospectively examined the possible effect of RT on PBPC collection. MATERIALS/METHODS We reviewed the charts of 732 MM patients (pts) seen from 1997-2016 at our institution and included pts who received RT prior to PBPC collection for planned ASCT. RT plans (both MM and non-MM RT) were reviewed to estimate the percentage (%) bone marrow (BM) treated using published estimates of skeletal BM distribution. Statistics were performed using Pearson correlations and t-tests. RESULTS Of 732 MM pts, ASCT was planned for 485 pts; of these, 223 pts received RT prior to PBPC collection and were included in the final cohort. 133 pts (60%) were male. Median age at PBPC collection was 59 years (range 33-80). For SIT, pts received combination regimens including the following agents: bortezomib (142 pts, 64%); lenalidomide (111 pts, 50%); alkylators (46 pts, 21%). Nine pts (4%) received dexamethasone alone. RT plans and/or a description of the fields, were available to estimate treated BM% for 221 pts. The median cumulative BM% treated per pt was 6.7 (range 0.0-47.4). The median RT dose was 24 Gy (range 10.0-75.6 Gy). Mobilization was performed using granulocyte-colony stimulating factor (G-CSF) alone (189 pts, 85%), G-CSF with plerixafor (15 pts, 7%), or chemotherapy (19 pts, 8%). PBPC collection data was available for 199 pts. A median of 7.8?×?10(6) CD34(+)/kg PBPCs (range 0.5-54.8) were collected in a median of 3 (1-9) apheresis procedures. 196 pts (99%) collected more than 2.0?×?10(6) CD34(+)/kg (minimum PBPC no. required for engraftment), and 167 pts (84%) collected more than 5.0?×?10(6) CD34(+)/kg (preferred no. of PBPCs collected). The number of PBPCs collected was not associated with BM% treated (P?=?0.15) or RT dose (P?=?0.56). The number of apheresis procedures performed was not associated with BM% treated (P?=?0.54) or RT dose (P?=?0.85). The number of PBPCs collected did not differ significantly for pts receiving RT to the pelvis (P?=?0.96), lumbar spine (P?=?0.35), or thoracic spine (P?=?0.059). Time to platelet engraftment was longer for patients with higher %BM treated (P?=?0.02). Eleven pts did not undergo a confirmed ASCT due to: pt preference (3 pts), trial therapy (1 pt), comorbidities (1 pt), election for hospice (1 pt), inadequate collection (4 pts) and inadequate follow up (1 pt). CONCLUSION Among pts with MM, RT prior to ASCT did not prevent adequate PBPC collection or impair successful ASCT. RT must be carefully planned and delivered to ensure safe incorporation into pre-ASCT treatment regimens.
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Busulfan and melphalan conditioning is superior to melphalan alone in autologous stem cell transplantation for high-risk MM
Saini, N., Bashir, Q., Milton, D. R., Tang, G., Delgado, R., Rondon, G., Popat, U. R., Hosing, C. M., Nieto, Y., Kebriaei, P., et al
Blood advances. 2020;4(19):4834-4837
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Impact of autologous transplantation in multiple myeloma patients with t(11;14): a propensity-score matched analysis
Saini, N. Y., Ma, J., Milton, D. R., Patel, R. D., Varma, A., Bashir, Q., Delgado, R. E., Tang, G., Rondon, G., Popat, U., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2019
Abstract
PURPOSE Multiple myeloma (MM) patients with t(11;14) have been considered to have standard-risk disease. However, several recent reports have shown contradictory results. We identified 95 MM patients with t(11;14) on Fluorescence In Situ Hybridization (FISH) studies, who underwent upfront autologous hematopoietic stem cell transplant (auto-HCT) at our center. We compared their outcome with a group of standard-risk MM patients who had diploid cytogenetics by both conventional cytogenetics (CC) and FISH (n=287). EXPERIMENTAL DESIGN To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis. A total of 160 patients, 80 in each group, were identified. RESULTS Patients in t(11;14) group had a post auto-HCT overall response rate (ORR) of 97.5%(78/80), compared to 100% (80/80) in the standard-risk control group (p=0.50). CR rate in the t(11;14) group was 35%(28/80), compared to 45%(36/80) in the standard-risk control group (p=0.26). The four-year PFS rates were 40.8% (95% CI: 29.6%-56.1%) and 51.1% (95%CI: 39.4%-66.3%) in the t(11;14) and standard-risk control groups, respectively (p=0.14). The four-year OS rates were 74.9% (95%CI: 63.3%-88.7%) and 88.3% (95%CI: 80.4%-97.0%) in the t(11;14) and standard-risk control groups, respectively(p=0.17). Also, patients with t(11;14) with concurrent cytogenetics had significantly poor PFS and OS compared to a propensity matched standard-risk control group. CONCLUSIONS Our study confirms that t(11;14) MM undergoing upfront autologous transplantation had similar outcomes as MM patients with normal cytogenetic and FISH studies. Existence of additional genomic aberrations by CC or FISH was associated with a worse outcome.
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Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial
Bashir, Q., Thall, P. F., Milton, D. R., Fox, P. S., Kawedia, J. D., Kebriaei, P., Shah, N., Patel, K., Andersson, B. S., Nieto, Y. L., et al
The Lancet. Haematology. 2019
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Editor's Choice
Abstract
BACKGROUND Retrospective studies suggest that conditioning therapy with busulfan plus melphalan could result in longer progression-free survival compared with melphalan alone in patients with multiple myeloma undergoing autologous haemopoietic cell transplantation (auto-HCT). We aimed to test this hypothesis in a randomised trial. METHODS The primary objective of the study was to compare progression-free survival with conditioning of busulfan plus melphalan with melphalan alone in patients with multiple myeloma. Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease, were randomly assigned (1:1) to treatment. Patients received either busulfan plus melphalan, with a test dose of busulfan 32 mg/m(2) followed by pharmacokinetically adjusted doses on days -7, -6, -5, and -4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m(2) per day on days -2 and -1 (total melphalan dose 140 mg/m(2)), or a melphalan dose of 200 mg/m(2) on day -2. Randomisation was performed via a Clinical Trial Conduct Website at the University of Texas MD Anderson Cancer Center. The accrual is complete and final results are presented here. The study is registered with ClinicalTrials.gov, number NCT01413178. FINDINGS Between Oct 12, 2011, and March 22, 2017, 205 patients were assessed for eligibility and randomly assigned to treatment. The primary analysis of progression-free survival was measured in 202 patients who received treatment: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. 90 days after auto-HCT, 102 (98%) of 104 patients given busulfan plus melphalan and 95 (97%) of 98 patients given melphalan alone achieved partial response or better. The median follow-up in the busulfan plus melphalan group was 22.6 months (IQR 15.2-47.1) and 20.2 months (IQR 8.8-46.6) in the melphalan alone group. Median progression-free survival was 64.7 months (32.9-64.7) with busulfan plus melphalan versus 43.5 months (19.9-not estimated) with melphalan alone (hazard ratio 0.53 [95% CI 0.30-0.91]; p=0.022). There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group. INTERPRETATION These findings, if confirmed in other ongoing studies, suggest that busulfan plus melphalan could replace melphalan alone as the conditioning regimen for auto-HCT in patients with newly diagnosed myeloma. FUNDING This study was funded in part by the National Institutes of Health (NIH) through MD Anderson's Cancer Center Support Grant (CA016672).
PICO Summary
Population
Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease (n=202)
Intervention
Busulfan plus mephalan conditioning prior to autologous transplantation (n=104)
Comparison
Melphalan conditioning alone (n=98)
Outcome
Median progression-free survival was 64.7 months with busulfan plus melphalan versus 43.5 months with melphalan alone. There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group.
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Outcome of Multiple Myeloma With Chromosome 1q Gain and 1p Deletion After Autologous Hematopoietic Stem Cell Transplantation: propensity-score matched analysis: Outcome of 1q+/1p- MM pts after auto-HCT
Varma, A., Sui, D., Milton, D. R., Tang, G., Saini, N., Hasan, O., Mukherjee, A., Joseph, J. J., Bashir, Q., Rondon, G., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
BACKGROUND The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. METHODS In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and auto-HCT. From January 2006 to December 2015, 1491 newly diagnosed MM patients underwent upfront high-dose therapy and auto-HCT at our institution. Out of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients, and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (N=287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above two cohorts, using a propensity-score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, international staging system stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen and maintenance therapy. RESULTS Sixty-seven (79%), 4 (5%) and 14 (16%) patients had 1q+, 1p- or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and control groups. The median follow-up time for all patients was 29.2 months (range: 0.29 -84.96). The cumulative incidence of 100-day non-relapse mortality was 1.2% and 0% for the 1q+/1p- and the control groups, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared to 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates for the 1q+/1p- and the control groups were 41% and 79%, and 56% and 86%, respectively. Patients in the 1q+/1p- group experienced significant increased risk of progression or death compared with the control group (HR 2.21, CI 1.18-4.16, P=0.014). No significant association between OS in the two groups were observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity-score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared to 38.8 months for the control group (HR 1.9, CI 0.9-4.08, P=0.09). The median OS had not reached for the 1q+1/p- alone subgroup and was 81.1 months for the control group (HR 1.25, CI 0.3-4.6, P=0.73) CONCLUSION 1q+/1p- abnormalities with amplification of CKS1B and deletion of CDKN2C genes were associated with shorter PFS when compared to a propensity-score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+1/p- MM patients have improved with the use of more effective induction, conditioning, and maintenance therapy compared to historical controls, but they still need more effective therapeutic approaches to fully overcome the negative impact of 1q+1/p-.
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A case control study of syngeneic transplantation versus autologous transplantation for multiple myeloma: two decades of experiences from a single center
Mohyuddin, G. R., Faisal, M. S., Badar, T., Shah, N., Bashir, Q., Patel, K. K., Hosing, C., Popat, U. R., Rondon, G., Delgado, R., et al
Leukemia & lymphoma. 2018;59(2):515-518
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Amifostine reduces gastro-intestinal toxicity after autologous transplantation for multiple myeloma
Malek, E., Gupta, V., Creger, R., Caimi, P., Vatsayan, A., Covut, F., Bashir, Q., Champlin, R., Delgado, R., Rondon, G., et al
Leukemia & lymphoma. 2018;59(8):1905-1912
Abstract
High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasome inhibitors and immunomodulatory drugs. Gastrointestinal (GI) toxicity is the main cause of morbidity after HDM. Amifostine, a cytoprotective agent, may reduce HDM-associated GI toxicity. We conducted a case control study comparing HDM + auto-HCT with or without amifostine for MM patients. One hundred and seven patients treated at University Hospitals Cleveland Medical Center who received pre-transplant amifostine were compared to 114 patients treated at MD Anderson Cancer Center without use of this agent. Amifostine 740 mg/m(2) was administered as a bolus infusion at 24 h and 15 min before HDM. Patients' characteristics were similar in both the groups. Amifostine therapy was well tolerated without any significant adverse effects. Grade II or greater oral mucositis (27.1% vs 47.4%; p = .002), nausea (31.8% vs. 86.0%; p = .0001), vomiting (18.7% vs. 52.6%; p = .0001) and diarrhea (56.1% vs. 72.7%; p = .006) occurred less frequently in the amifostine-treated group. There was no discernable effect of amifostine on engraftment, progression-free or overall survival. Our results indicate that amifostine decreases GI toxicity while preserving anti-myeloma efficacy of HDM and auto-HCT.
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Modified CVAD and modified CBAD compared to high-dose cyclophosphamide for peripheral blood stem cell mobilization in patients with multiple myeloma
Gettys, S. C., Gulbis, A., Wilhelm, K., Sasaki, K., Dinh, Y., Rondon, G., Qazilbash, M. H.
European Journal of Haematology. 2017;98(4):388-392
Abstract
BACKGROUND The optimal regimen for peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) has not been established. Experience at The University of Texas MD Anderson Cancer Center suggests in addition to single-agent cyclophosphamide (Cy), modified cyclophosphamide, vincristine, doxorubicin, and dexamethasone (mCVAD), and modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone (mCBAD) may be successful chemomobilization regimens. METHODS This retrospective review included 167 patients (66 with Cy, 74 with mCVAD, and 27 with mCBAD) with multiple myeloma undergoing mobilization for auto-HCT between January 1, 2006 and September 30, 2013. The primary objective was to evaluate and compare the successful mobilization of CD34+ cells among high-dose Cy, mCVAD or mCBAD. RESULTS Successful mobilization (>=2x106 CD34+ cells/kg) was achieved in all patients, while 65 (98%), 72 (97%), and 27 (100%) patients achieved an optimal mobilization (>=4x106 CD34+ cells/kg) in the Cy, mCVAD, and mCBAD groups, respectively. There was no significant difference in the number of apheresis sessions (P=.63), incidence of febrile neutropenia (P=.57), or hospital admission rates (P=.55). CONCLUSION Either Cy, mCVAD, or mCBAD can yield successful PBSC mobilization in patients with multiple myeloma undergoing auto-HCT. Copyright © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.