High Dose BCNU/Melphalan Preparative Regimen Doubles Event Free Survival of Myeloma Patients Undergoing Autologous Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2012-2012
Author(s):  
Cristina Gasparetto ◽  
Wendi A. Bacon ◽  
Phuong Doan ◽  
David A. Rizzieri ◽  
Mitchell E. Horwitz ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Conditioning Regimen ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Event Free Survival ◽  
Free Survival ◽  
Preparative Regimen ◽  
Related Mortality

Abstract Abstract 2012 High dose chemotherapy (HDC) followed by autologous stem cell transplant (ASCT) remains a valid treatment option for patients with multiple myeloma (MM). HDC has improved response rate, event-free survival (EFS) and treatment free interval for patients with MM when compared with conventional chemotherapy. To date, Melphalan 200 mg/m2 (HDM) remains the standard ASCT preparative regimen as no other regimens have demonstrated improved outcomes with acceptable toxicity. Nevertheless, relapse remains inevitable with this approach prompting continued search for better therapies. To overcome resistance and early relapse we used a more aggressive alkylator based conditioning regimen. Here we summarize a retrospective study of the long-term follow-up of newly diagnosed MM patients treated with the preparative regimen Carmustine, 500 mg/m2 and Melphalan, 200 mg/m2 (BCNU/HDM) followed by ASCT versus a subsequent group of patients treated with HDM alone and ASCT. Methods: Between November of 1997 and December of 2008, 207 patients with MM underwent HDC followed by ASCT at our Institution, using either BCNU/HDM (n = 104, treated between 1997–2002) or HDM (n = 103, treated between 2002–2008) as the preparative regimen. Presenting patient characteristics were similar (age, gender, MM type, hemoglobin, creatinine, calcium, plasma cell infiltration, Durie-Salmon stage, and ISS stage). Patients treated with BCNU/HDM were diagnosed preceding the introduction of novel anti-MM agents such as thalidomide, lenalidomide, and bortezomib and thus did not receive these as induction therapy, while HDM patients received various combinations of novel agents as induction therapy. Results: With a median follow-up for surviving patients of 96 and 34 months for the BCNU/HDM and HDM cohorts, respectively, the event-free survival (EFS) was significantly increased with the BCNU/HDM conditioning regimen (41.7 months) as compared with the HDM regimen (21.6 months, p = 0.013) (Figure 1). Median overall survival (OS) was 83.1 months with BCNU/HDM vs. 68.2 months with HDM (p = 0.359 at current follow-up) with 34% of BCNU/HDM patients alive at >10 years (Figure 2). In the BCNU/HDM group, 47/104 patients achieved ≥VGPR and this subgroup had a median OS of 103 months. Nineteen patients in the BCNU/HDM group are ≥7 years from ASCT and 18 (17%) have never required treatment for progressive disease. Engraftment and transplant-related mortality were similar in both groups (3% TRM in the BCNU/HDM and 4% TRM in the HDM arm). The BCNU/HDM group had a higher incidence of pneumonitis (50%) vs. the HDM group (15%) but this was managed with short courses of steroids and was never fatal. Focusing on the subgroup of patients who proceeded to transplant immediately after only 1 induction course, the median OS was 103 months for the BCNU (80 patients) containing arm versus 69 months for the HDM (71 patients) arm (p=0.085), suggesting a clear trend further favoring this dose dense approach. Conclusions: EFS was superior with the BCNU/HDM regimen compared with HDM and a subgroup of patients treated with BCNU/HDM have achieved EFS >7 years without any additional therapy. Engraftment and treatment related mortality were similar in both groups despite advances in supportive care for the HDM group. Our findings suggest that BCNU/HDM should be compared in a randomized prospective fashion to HDM as an ASCT preparative regimen following optimal induction therapy with novel agents to determine whether this will lead to further improvements in EFS and OS following ASCT. Disclosures: No relevant conflicts of interest to declare.

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1163-1163
Author(s):  
Sam O. Wanko ◽  
Jon P. Gocherman ◽  
Joseph O. Moore ◽  
Carlos Decastro ◽  
Robert Prosnitz ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Mantle Cell ◽  
Dose Dense

Abstract BACKGROUND: Mantle cell lymphoma (MCL) typically has a poor outcome with overall survival of only 3–4 years. Higher treatment response and event-free survival has been demonstrated with aggressive high dose chemotherapy followed by autologous hematopoietic stem cell support, though long term cure rates remain unclear(Dreger P. Hematol J. 2000;vol.2). Modest response rates have also been reported with the monoclonal antibody (MoAb) rituximab and ALEMTUZUMAB (Foran, JM. JCO 2000; vol. 2. Faderl S. Blood 2003; vol. 9). We therefore combined dose-dense therapy with MoAbs to explore response rate and event free survival (EFS) in mantle cell lymphoma. The strength of this trial design is ability to follow all patients from induction chemotherapy through high dose therapy and transplant in order to gauge clinical outcome on all enrolled patients, not just the subpopulation who is able to proceed to high dose therapy. PATIENTS AND METHODS: Induction therapy consisted of 1 cycle of high dose cytarabine (3gm/m2 IV over 1 hour Q12H for 8 doses), mitoxantrone (10mg/m2 daily for 3 days), and ALEMTUZUMAB 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg over 2 hours day -6, etoposide 60mg/kg over 4 hours day -4, and cyclophosphamide 100mg/kg over 2 hours day -2 followed by autologous reinfusion on day zero. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant. RESULT: 9 patients with advanced disease (7 stage IV, 1 stage III, 1 stage IIA) and median age of 60 (48 – 65 years) have been accrued and treated since February 2003. Four were newly diagnosed and 5 had relapsed/refractory disease. Seventy eight percent (7/9) had complete response and 22% (2/9) had partial response (PR) following induction therapy. One patient had severe infection after induction and was unable to proceed to transplant. Another had constitutional decline preventing further therapy and each died within 4 months of withdrawal from the protocol. Both had relapse/refractory disease at accrual. The remaining 7 patients proceeded to the transplant phase. With a median follow-up of 7 months (range 3–16 months), all 7 patients remain in CR for 1 –16 months. Significant induction therapy toxicity included neutropenia in all 9 patients with average duration of 10.7 days, non-disseminated CMV reactivation in 44% of patients, one overwhelming fungal infection, and one patient with delay in engraftment. Figure Figure CONCLUSION: Our preliminary data show a high induction and transplant phase completion rate, manageable toxicity, and excellent overall response rate in this group of elderly patients with advanced disease. Larger numbers of patients and longer follow-up is needed to confirm these promising results.

Characteristics Of Multiple Myeloma Patients With 6-Year Or Longer Progression-Free Survival After a Single Autologous Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3366-3366 ◽  
Author(s):  
Kehinde U.A. Adekola ◽  
Qaiser Bashir ◽  
Nina Shah ◽  
Sai Ravi Pingali ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Survival ◽  
Autologous Transplant ◽  
Preparative Regimen

Background High dose chemotherapy followed by an autologous stem cell transplant (auto-HCT) is considered standard of care in patients with newly diagnosed multiple myeloma (MM). In a recent randomized trial, median progression free survival (PFS) after auto-HCT, with or without maintenance therapy was 46 and 27 months, respectively (McCarthy P et al. NEJM 2012). However, about 15% of patients are reported to have much longer PFS (Pineda-Roman M et al. Cancer 2008). Here we tried to identify the factors that may predict a long PFS after auto-HCT. Methods We performed a retrospective chart review of patients who received an auto-HCT for MM between January 2000 and March 2007. A total of 1135 patients underwent an auto-HCT during this period, and 194 patients (17%) had a minimum PFS of 72 months or longer after a single auto-HCT. The primary objective was to determine the variables associated with a long PFS and overall survival (OS). Results Patient characteristics and outcomes are shown in the attached Table. The median age at auto-HCT was 56 years, and the median time from diagnosis to auto-HCT was 7.5 months. Twenty-three (13%) patients had ≥ 10% plasma cells in the bone marrow at auto-HCT and only 9 patients (4.8%) had high-risk cytogenetic abnormalities. One-hundred and fifty (77%) patients received induction therapy containing either an immunomodulatory (IMiD) agent or a proteasome inhibitor (PI). At the time of the auto-HSCT, only 13 (6.7%) patients were in CR and 38 (19.6%) were CR or VGPR after induction therapy (Table). One-hundred and sixty three (84%) patients received mephalan alone as conditioning regimen. Eighty-one (42%) patients received post auto-HCT maintenance. Eighty (41%) patients achieved a CR, while 104 (54%) achieved CR + VGPR after auto-HCT. Six patients (3.1%) developed a second primary malignancy post- autologous transplant. After a median follow-up of 95.4 months, median PFS was 97.3 months and median OS has not been reached. The 10-year PFS and OS were 41% and 73% respectively. Use of melphalan alone as preparative regimen was associated with a longer PFS and OS (p=0.004 and 0.004, respectively). Achievement of CR after auto-HCT was associated with a longer PFS only (p=0.001), and the use of IMiD or a PI as induction was associated with a longer OS (p=0.01). Conclusion Approximately 17% patients achieved a median PFS of 6 years or longer after a single auto-HCT. The long PFS in this cohort may be associated with younger age, low incidence of HR cytogenetics, use of an IMiD or PI as induction therapy, relatively low disease burden at auto-HCT, transplant from the year 2000 onwards, achievement of CR in >40% and the use of melphalan alone as preparative regimen. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees.

A Multicenter Comparison of Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation with Tandem Autologous Stem Cell Transplantation in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 940-940 ◽  
Author(s):  
Chang-Ki Min ◽  
Hwak Kim ◽  
Kihyun Kim ◽  
Jae-Yong Kwak ◽  
Seung Tae Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Induction Treatment ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Related Mortality

Abstract Background: Autologous stem-cell transplantation (ASCT) after high-dose chemotherapy is regarded as the standard therapeutic approach for multiple myeloma (MM) even if virtually all patients ultimately relapse following this procedure. Recently, tandem ASCT significantly improved overall survival (OS) and event-free survival (EFS) compared with single ASCT. Another strategy is to use reduced-intensity allogeneic stem cell transplantation (RISCT) earlier in the course of disease in chemosensitive patients. In the current study, we retrospectively analyzed the outcomes after a planned tandem ASCT or RISCT in the patients who previously underwent ASCT. Patients and methods: One-hundred twenty-six patients who received a high dose (140 to 200 mg/m2) of melphalan as the conditioning regimen of the first ASCT were analyzed. Ninety-six patients (median age, 50.5 years) received a second ASCT, whereas 30 patients (median age, 46.5 years) underwent a RISCT (related in 28 patients and unrelated in 2 patients). The median interval between the first and second transplant was 131 days in tandem ASCT group and 157.5 days in RISCT group. The conditioning regimen for the tandem ASCT and RISCT consisted of high-dose melphalan ± total body irradiation (TBI) and fludarabine + melphalan or TBI, respectively. The two groups were evenly matched with regard to other disease characteristics. Results: After a median follow-up of 664 days (range, 143–2904) from the first ASCT, the median event-free survival (EFS) and overall survival (OS) in all 126 patients were 878 days and 1838 days, respectively. The median EFS in the second ASCT vs. RISCT group were 844 days (95% CI, 714–973) and 1342 days (95% CI, 813–1870), respectively (P=0.262). The median OS in the tandem ASCT vs. RISCT group were 2160 days (95% CI, 1847–2832) and 1575 days (95% CI, 1202–1947), respectively (P=0.132). Disease-related mortality was not significantly different between the second ASCT vs. RISCT groups (73.3% vs. 60.0%, P=0.325) as well as treatment-related mortality between the 2 groups (26.7% vs. 40%, P=0.358). On multivariate analysis, an achieving a good response (≥ VGPR) after the induction treatment predicted a better EFS compared to a poor response (≤ PR) (RR; 0.245, P=0.01). A good response after first ASCT or the second transplant was associated with a better EFS by univariate analysis but not by multivariate analysis (RR; 0.927, P=0.830 or RR; 0.772, P=0.453, respectively). Conclusion: In this retrospective analysis, ASCT followed by RISCT was not superior to the tandem ASCT, either EFS or OS. Disease-related deaths were not different between the 2 groups. Patients whose disease is sensitive to induction chemotherapy and who obtain a good response after the induction treatment benefited the most from this tandem transplant therapy.

Stem Cell Transplant in Multiple Myeloma: Impact of Response Failure in the Era of Novel Therapies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1878-1878
Author(s):  
Morie A Gertz ◽  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
David Dingli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Novel Agent

Abstract Abstract 1878 Poster Board I-900 Autologous stem cell transplant as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplant. Previously published medical literature has showed that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplant. With the introduction of novel agents—immunomodulatory drugs and proteasome inhibitors—response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response after induction therapy with a regimen that contains a novel agent. Unlike patients in reports published previously—before novel agents—patients who do not achieve partial remission have a significantly shorter overall survival from transplant (74.0 vs 43.5 months) and a shorter progression-free survival (22.6 vs 13.1 months; P<.001). Absence of a response to induction therapy with a novel agent predicts a poorer outcome after high-dose therapy.{abstabft}.b CR+VGPR for plateau, P<.001 compared with other 3 categories. Failure to respond to novel-agent induction leads to shorter posttransplant progression-free survival (PFS). Failure to respond to novel-agent induction leads to shorter posttransplant overall survivalDisclosures: Gertz: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kumar: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Lacy: celgene: Honoraria; millenium: Honoraria.TableMultivariable Analysis of Posttransplant Progression-Free SurvivalVariableP ValuePlateau vs relapsed-refractory.003Albumin.86Sex.94b2-Microglobulin.89Bone marrow plasma cells.18Age.75Abnormal cytogenetics.002CTX mobilization.51Labeling index.002

Busulfan Area-under-the-Curve Finding Study within a Busulfan/Fludarabine (BuFlu) Conditioning Regimen before Allogeneic Hematopoietic Cell Transplantation (HCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2939-2939 ◽  
Author(s):  
Teresa Field ◽  
Janelle Perkins ◽  
Melissa Alsina ◽  
Ernesto Ayala ◽  
Karen Fancher ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Systemic Exposure ◽  
Pharmacokinetic Analysis ◽  
Event Free Survival ◽  
Free Survival ◽  
Unrelated Donors ◽  
M Estimates ◽  
Related Mortality

Abstract Relapse of malignancy is frequent in patients transplanted with advanced diseases. There is a relationship between higher Bu exposure and lower risk of relapse, but also higher transplant-related mortality, and data indicated the maximum tolerated daily Bu AUC is < 6000 microMol/min when Bu is used in combination with cyclophosphamide (Cy). To reduce transplant-related mortality, Flu has been substituted for Cy in many transplant centers. We hypothesized that pharmacokinetics-targeting of IV Bu, which results in a predictable systemic exposure, would produce values of tolerable Bu AUC that are higher for BuFlu than for BuCy. Our standard HCT regimen since July 2004 consists of once daily IV BuFlu where fludarabine 40 mg/m2 is given intravenously daily for four days and each infusion is followed immediately by an initial IV Bu dose of 130 mg/m2. Pharmacokinetic analysis is performed after the first infusion of busulfan; the goal is to adjust the busulfan doses for days 3 and 4 to achieve an average exposure targeted to an AUC of 4500–5600 microMol/min. Outcomes for the first sixty-nine patients were analyzed. Thirty-nine of 63 (62%) evaluable patients had their Bu doses adjusted, 30 increased [median adjustment 50% (8 – 175%)], and 9 decreased [median 30% (11 – 60%)], while 24 (38%) pts had an AUC within the desired range without adjustment. Most of the patients (98%) had hematological malignancies and 73% had high CIBMTR risk, median age was 48 (22–68) years, donors were HLA-identical siblings (33), matched (23) or mismatched unrelated donors (13). With a median patient follow-up of 392 (248 – 707) days, the non-relapse mortality was 4% at 100 days and 17% at one year. The K-M estimates of survival and event-free survival are 88%±4% and 83%±5% at 100 days, and 61%±6% and 51%±6% at 1 year, respectively. Subsequently, as part of a prospective, targeted AUC-dose finding trial, 20 patients received an initial Bu dose of 170 mg/m2 with subsequent doses targeted to achieve a 4-day average AUC of 5400–6600 microMol/min. Pharmacokinetic analysis was performed after the first and fourth infusion of busulfan. All patients had hematologic malignancies, 65% had high CIBMTR risk, median age was 48 (22 – 61) years, donors were HLA-A, B, C, DRB1, DQB1 matched siblings (11) or matched unrelated donors (9). Thirteen (65%) patients had their doses adjusted, six had it increased [median 37.1% (35.6 – 61.9 %)] and seven decreased [median 41.6% (18.3 – 55.2%)], while seven patients had an AUC within the desired range without adjustment. With a median follow-up of 111 (range 21–312) days, the 100-day K-M estimates of survival are 88%±8% and event-free survival 83%±9%. The complete observation of 100-day safety, relapse and survival will be presented at the meeting and data will determine further AUC escalation.

Fludarabine and Melphalan Conditioning Regimen in Young Patients with Acute Myeloid Leukemia in CR1 Undergoing a Matched Related Allogeneic Stem Cell Transplant: A Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5049-5049 ◽  
Author(s):  
Mammen Chandy ◽  
Vikram Mathews ◽  
T. Rajasekar ◽  
Kavitha M. Lakshmi ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Young Adults ◽  
Clinical Outcomes ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Young Patients ◽  
Cell Transplant ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Abstract Allogeneic SCT remains the most effective anti-leukemic therapy. However, due to the associated TRM with conventional myeloablative regimens, this has often not translated to a significant improvement in EFS or OS. Since October 2005, at our center, we offered a RIC regimen consisting of fludarabine 30mg/m2 x 5days followed by one dose of melphalan 140mg/m2 for young adults with AML in CR1 after induction chemotherapy. GVHD prophylaxis consisted of cyclosporine with a low dose short course methotrexate. The graft source was a PBSC harvest. The clinical outcomes were compared with a historical control who received a conventional Bu/Cy regimen. Since October 1992, 55 of patients with AML in CR1 (constituted 47% of all AML transplants done at our center) underwent a matched related allogeneic SCT. Among these 11 received a Flu/Mel conditioning regimen while 41 received a conventional Bu/Cy conditioning regimen (3 patients excluded from analysis since they received other conditioning regimens), the clinical outcomes of these two groups were compared. All, except for one donor (one antigen mismatch) in the Bu/Cy group, were complete 6/6 HLA identical related donors. The age (mean±SD) of patients in the Flu/Mel and the Bu/Cy group was 39±14 and 27±11 respectively. The baseline characteristics of these two groups were comparable for sex, donor age, female to male transplants, AML subtypes and requirement of two course of chemotherapy to achieve CR1. Four (36.4%) of patients among the Flu/Mel group and 28 (68.3%) in the Bu/Cy group received one or two cycles of consolidation chemotherapy prior to SCT. All patients in the Flu/Mel group received a PBSC graft while only 26 (41%) among the Bu/Cy group received a PBSC graft (P=0.05). One patient in the Bu/Cy group failed to engraft. All other cases engrafted. All 11 (100%) cases in the Flu/Mel group had a complete donor chimerism documented on day 30. Prophylactic donor lymphocyte infusion was not administered for any patient. There were no treatment related deaths in the Flu/Mel group up to day 100. One patient died on day 299 following pulmonary GVHD and septicemia. In comparison, the day 100 TRM was 8 (19.5%), going up to a one year all cause mortality of 21 (51%) in the Bu/Cy group. Acute GVHD grade 2–4 occurred in 5 (45.5%) and in 14 (34.1%) among patients conditioned with Flu/Mel and Bu/Cy, respectively. Chronic GVHD occurred in 4 (36.4%) of patients conditioned with Flu/Mel and was similar to the incidence seen in the Bu/Cy group. During the period of follow up none of the patients in the Flu/Mel group have relapsed while 11 (26.8%) patients had relapsed in the Bu/Cy group. The 2 year Kaplan-Meier estimate of EFS and OS for the Flu/Mel and Bu/Cy group (mean follow up 19 and 71 months, respectively) was 85.71±13.23 vs. 43.19±7.82 (P=0.0176) and 85.71±13.23 vs. 45.59±7.86 (P=0.027) respectively. A conditioning regimen of fludarabine and melphalan in young adults with AML in CR1 is associated with a low TRM with a potential to translate into improved EFS and OS. Figure 1: Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41) Figure 1:. Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41)

Analysis of Beam (Carmustine, Etoposide, Cytosine Arabinoside, Melphalan) Versus High Dose Melphalan (HDM) with Autologous Rescue in Multiple Myeloma(MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5227-5227 ◽  
Author(s):  
Karthikeyan A. Ramasamy ◽  
Ruth Branford ◽  
Radha Selvaratnam ◽  
Aloysius Y.L. Ho ◽  
Rafael Duarte ◽  
...  
Keyword(s):  
Stem Cell ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Significant Prolongation ◽  
Disease Free

Abstract Autologous stem cell transplantation is an established treatment that leads to prolongation in overall and disease free survival in MM. BEAM and M have been widely used as conditioning regimen for autologous stem cell transplant (ASCT) in patients with MM. At our centre MM patients with low creatinine clearance (Crcl) and a low performance status were offered Melphalan only as conditioning regime for ASCT. We report on our experience of HDM in comparison with standard BEAM. Records of 53 consecutive patients who had ASCT for myeloma at our centre between 2000 and 2003 were examined. Patients were staged as per Salmon and Durie (SD) criteria and EBMT response criteria were used for assessment post transplant .35 patients had BEAM conditioning (SD criteria 31-IIIA, 3-IA, 1-IIA) and 18(SD criteria 14- IIIA, 4-IIIB) had M.).Patients who received BEAM had a median age of 55 (range 38–66), median follow up of 19 months and those who received HDM had a median age of 60 (range 45 –69), follow up of 20.5 months. Stem cell source was peripheral blood (PBSC) in 50 patients, 1 Bone marrow (BM), and 2 BM and PBSC. HDM at a Dosage of 140 –200 mg/m2was administered in all HDM cases except for 1 patient who had 70mg/m2 because of Crcl of 17.4 ml/min. BEAM group had Carmustine 300mg/m2 (−6), Ara- C 800mg/m2 (−5 to −2), Etoposide 800mg/m2 (−5 to −2), M 140mg/m2 (−1). Patients in the M group had significantly lower haemoglobin and higher serum creatinine levels in comparison with the BEAM group. The 100-day treatment related mortality (TRM) was 5.5 % in HDM group, which was comparable to 2.2 % in the BEAM group. 9 out of 18 patients who had HDM relapsed and 9 out of 35 patients who had BEAM relapsed at follow up with Median relapse free survival (RFS) being 575 days in HDM group and has not achieved yet in BEAM group (p= .017). This data confirm that BEAM ASCT lead to significant prolongation of disease free survival with low TRM.Our data also suggest the effectiveness of HDM in patients who because of poor performance status and/or abnormal renal function may not tolerate BEAM ASCT

Treatment Outcome and Prognostic Factors for Infants With Acute Lymphoblastic Leukemia Treated on Two Consecutive Trials of the Children's Cancer Group

1999 ◽  
Vol 17 (2) ◽  
pp. 445-445 ◽  
Author(s):  
Gregory H. Reaman ◽  
Richard Sposto ◽  
Martha G. Sensel ◽  
Beverly J. Lange ◽  
James H. Feusner ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Historical Controls

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (> 95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG-1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG-1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/μL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG-1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

Holmium-166 (166Ho)-DOTMP Skeletal Targeted Radiotherapy (STR™) with Melphalan and Autologous Peripheral Stem Cell Transplant (PBSCT) for Multiple Myeloma (MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 922-922 ◽  
Author(s):  
Mark Goodman ◽  
William I. Bensinger ◽  
Sergio Giralt ◽  
Donna Salzman ◽  
Katherine L. Ruffner ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Complete Response ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Red Marrow

Abstract Background: 166Ho-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high dose radiation both to the bone and bone marrow. Follow-up data from 3 clinical trials with STR as conditioning for patients with MM undergoing autologous PBSCT are presented. Methods: In 2 Phase I/II dose-escalation trials, 83 patients received a dose of 166Ho-DOTMP STR calculated to deliver 20, 30, or 40 Gy to the red marrow; 82 pts received melphalan (140 or 200 mg/m2) ± 8 Gy TBI (n=25), followed by PBSCT. As of June, 2004, 77 subjects have been followed for at least 48 months. In a separate Phase II dosimetry trial, 12 patients received two 30 mCi tracer doses of 166Ho-DOTMP STR to determine the reproducibility of biodistribution and pharmacokinetics (PK). All pts received a 25 Gy therapy dose with concurrent IV hydration and continuous bladder irrigation, followed by 200 mg/m2 melphalan and PBSCT. These patients have been followed for at least 18 months. Results: Up to 2.3 Ci/m2, 166Ho-DOTMP STR was given in the Phase I/II trials; 29/83 (35%) patients achieved complete response (CR) and overall response rate (CR + PR) was 64% (7 pts not evaluable). The Kaplan-Meier estimate of median survival is 5.2 years for all 83 patients. In patients who are at least 4 years post transplant who achieved a CR, the survival is 74% (n=27). In patients who achieved less than a CR at least 4 years ago, the survival is 34% (n=44). Dose-related radiation-induced kidney toxicity presented in some patients more than 6 months post-therapy. The dose of 166Ho-DOTMP STR in the Phase II dosimetry trial was 550 to 860 mCi/m2, 166Ho-DOTMP. Currently, 18 months of follow-up reveals no occurrence of hemorrhagic cystitis or > Grade 2 elevated creatinine. A CR rate of 17% with an overall survival of 92%, was observed. In 10 patients who received 166Ho-DOTMP STR 750 mCi/m2 ± 10% in the Phase I/II trial, the CR rate was 40%, and the 4-year survival was 70%. Monitoring for safety and duration of response is ongoing in all 3 trials. Conclusion: Follow-up from the Phase I/II trials confirms that 166Ho-DOTMP STR provides favorable efficacy and safety as part of the conditioning regimen for patients with MM undergoing PBSCT. A Phase III, randomized multicenter study is now open to enrollment, comparing the safety and efficacy of 166Ho-DOTMP STR plus melphalan to melphalan alone as conditioning for PBSCT in subjects with primary refractory MM who have failed to respond to induction therapy, including high-dose dexamethasone, and are within 18 months of diagnosis.

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