Long-Term Follow-up of Patients With Multiple Myeloma Who Received Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2154-2154
Author(s):  
Michele L. Donato ◽  
David S Siegel ◽  
David H. Vesole ◽  
Phyllis McKiernan ◽  
Themba Nyirenda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematopoietic Stem ◽  
Unrelated Donors

Abstract Allogeneic transplantation for multiple myeloma (mm), although seen as potentially curative, has inherent treatment-related mortality and long-term implications. Important questions remain such as the expectation for long-term survival and the role, if any, of the graft versus tumor effect. The study cohort included 56 consecutive patients (pts) with mm who received an allogeneic hematopoietic stem cell transplant (HSCT) between November 9, 2004 and June 1st 2011. Only pts who had received at least one prior autologous transplant were included in this retrospective analysis. Patients received either a non-myeloablative (NMA), a reduced intensity (RIC) or an ablative (MA) regimen. The NMA regimen consisted of low dose TBI for siblings and low dose TBI with fludarabine for unrelated donors. The RIC regimen was fludarabine melphalan, with the addition of low dose thymoglobulin for unrelated donors. The MA regimen was busulfan and melphalan, with thymoglobulin for unrelated donors. A favorable group of 26 pts received their allogeneic transplantation for consolidation after demonstrating a response (PR, VGPR, CR) to their prior autograft and without evidence of progression, leaving 30 pts in the salvage transplant group defined as pts unresponsive (less than PR) or with relapse after their prior autograft. The median age was 52.4 years (SD = 6.9 years). Twenty six (46%) pts were female. The hematopoietic cell donors were 35 siblings and 21 unrelated (URD). In the URD group, 10 (47.6%) pts had a mismatched donor. In our cohort 10 (17.9%) pts received a MA, 22 (39.3%) received a RIC and 24 (42.9%) received a NMA regimen. The median follow-up was 52 months. The related and unrelated donor cohorts were similar except for age (53.9 years versus 49.8 years p = 0.03). Overall, 32 (57.1%) pts achieved a CR. Seven (12.5%) pts had a VGPR, 13 (23.2%) had a PR and 2 (3.6%) had stable disease. At the time of analysis, 49.2% of pts were in CR. Twenty one (37.5%) pts relapsed post transplantation of whom 16 received donor lymphocytes (DLI 15 pts) or immune suppression withdrawal (1 pt), with 10 (62.5%) pts responding to this intervention. The cumulative incidence of acute GVHD (aGVHD) grade II-IV was 35.4%, 28.6% for related donors and 47.6% for URD (p = 0.16). The cumulative incidence of chronic GVHD (cGVHD) was 50%, 52% for related donors and 43% for URD (p=NS). The number of non-relapse deaths (NRM) was 13 (23.2%). The cumulative incidence of NRM at 1 year was 18.2%, and 25.5% at 5 years. In the multivariate model, number of prior autologous HSCT (1 vs >1) and grade III-IV aGVHD were significantly associated with an increased NRM. The overall survival (OS) for all 56 pts was 59% at 5 years. The OS at 5 years for the 30 pts who received transplantation as salvage (refractory to the prior autograft or relapsed after the prior autograft), was 38% compared to 82% for the consolidation group. The univariate analysis indicates that pts receiving their allogeneic transplantation as salvage, disease status prior to allogeneic HSCT, number of prior auto HSCT, aGVHD, response post allo HSCT and cGVHD were significantly associated with the risk of all cause mortality, with cGVHD being protective. Donor type (URD versus related), adverse cytogenetics, preparative regimen and age were not significant predictors of risk for all cause mortality by univariate analysis.Overall survival salvage (yes) vs consolidation group (no)Overall survival salvage (yes) vs consolidation group (no)Overall survival pts with (yes) or without (no) chronic GVHDOverall survival pts with (yes) or without (no) chronic GVHD Multivariate analysis shows OS significance for being in the salvage group (HR 4.05, p=0.0196), a GVHD (HR 2.99, p=0.034) and cGVHD (HR 0.26, p=0.012), the latter being protective. The PFS for all 56 pts was 38% at 5 years, 57% for the consolidation group and 21% for the salvage group. In conclusion, patients with multiple myeloma can have an excellent overall survival following allogeneic transplantation even in the setting of relapsed or refractory disease to a prior auto HSCT. Unrelated donors performed just as well as matched siblings. Acute GVHD was deleterious to OS, whereas chronic GVHD was significantly associated with improvement in OS supporting the role of a graft versus tumor effect in multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Encouraging Outcomes in African-American Patients with Use of Post-Transplant Cyclophosphamide after HLA Mismatched Hematopoietic Stem Cell Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3228-3228
Author(s):  
David H. Aggen ◽  
Kendra Mellert ◽  
Divaya Bhutani ◽  
Lois Ayash ◽  
Lawrence G. Lum ◽  
...  
Keyword(s):  
Overall Survival ◽  
African American ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Equity Ownership

Abstract An inherent difficulty in performing allogeneic transplantation in patients (pts) of African American (AA) descent is finding suitably matched 8/8 unrelated donors. In addition for complicated reasons studies have shown that AA have an inferior survival compared to suitable matched patients from different ethnic groups undergoing allogeneic transplantation. Post transplant cyclophosphamide (PTCy) administered on day + 3 and +4 given in combination with tacrolimus and mycophenolate mofetil (MMF) allows for the safe use of more mismatched transplants, including haploidentical transplants. This has created a new approach for patients who lack suitable donors and may allow more AA pts to proceed to transplant. At our institution, we have used PTCy as graft-versus-host-disease (GVHD) prophylaxis in patients undergoing reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) from mismatched related and unrelated donors, and this group consisted largely of high-risk AA pts. We retrospectively reviewed 16 pts who underwent HLA mismatched HSCT (5/10 to 8/10 HLA matches) at our institution between July 2012 and 2015. All patients received RIC HSCT with PTCy (days +3 and +4) along with tacrolimus and MMF for GVHD prophylaxis. Patients did not routinely receive growth factor support. Primary endpoints included time to neutrophil and platelet engraftment, length of hospital stay, and rates of acute and chronic GVHD. Secondary outcomes included time to relapse, transplant related mortality, and overall survival. Table 1 shows the demographics of the 16 patients who were transplanted. The median age of the patients was 57 years (range: 25-72). Ten pts were of AA descent. Fifteen donors were haploidentical family donors; 6 were 5/10 matches, 4 were 6/10 matches, and 5 were 7/10 matches. One patient received a 8/10 unrelated donor transplant. Five patients had failed previous transplants which included 3 allogeneic and 2 autologous HSCT. Based on published risk stratification (Armand et al. Blood, 2012) of the remaining 11 pts, 7 pts were high risk and 4 were intermediate risk. Neutrophil engraftment (first of 3 days when ANC was ³500 cells/mm3) occurred a median of 19 days post transplant (range:12-22 days); Platelet engraftment (³20,000/µL without platelet transfusion) occurred a median of 21.5 days post-transplant (range: 14-37 days). Median length of hospitalization was 26 days (range: 22-81 days). Two pts failed to engraft after first HSCT. One of these pts had high levels of anti-HLA antibodies directed against her donor. Both pts went on to a second haploidentical transplant and engrafted their neutrophil counts at 13 days and 21 days; respectively. Grade II acute GVHD occurred in 6/16 patients. No patient developed grade III-IV aGVHD. Chronic GVHD was observed in 8/16 patients with severe chronic GVHD seen in one patient. With a median follow up of 160 days (range: 89-778 days) the Kaplan-Meier estimates of overall survival at one year were 81.3% for all transplanted pts (Figure 1) and 80% for the AA pts (Figure 2). Three pts died; 1 patient from an invasive fungal infection and 2 pts from relapse. One additional patient relapsed but continues on treatment. Our experience suggests that the use of PTCy permits HLA mismatched transplantation, with overall survival of > 80% and acceptable rates of acute and chronic GVHD. Moreover, the severity of acute GVHD in patients who received PTCy post-transplant was limited, with no reported acute grade III-IV GVHD. In addition, the early outcomes of HLA mismatched transplantation in 10 African-American patients, a population that is often underrepresented in the donor registry, suggests that this approach may preferentially benefit AA pts from an expanded donor pool derived from utilization of partially HLA-matched donors. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Lum: Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding.

Outcome of BEAM-Autologous and BEAM-Alemtuzumab Allogeneic Transplantation in Relapsed Advanced Stage Follicular Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2022-2022
Author(s):  
Victor Noriega ◽  
Anjum Bashir Khan ◽  
Stephen Devereux ◽  
Robert E. Marcus ◽  
Michelle Kenyon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
High Grade ◽  
Advanced Stage

Abstract Abstract 2022 Introduction: Follicular Lymphoma is the most common indolent lymphoma, characterized by an indolent course, multiple recurrence, responses to chemotherapy, risk of transformation into a high grade lymphoma and with a median overall survival of 10–12 years. Transplantation (autologous and allogeneic) has improved the overall outcome of this disease, however a continuous pattern of relapse is observed essentially in the autologous setting. Allogeneic transplant has shown encouraging results in terms of long term overall survival (OS) and disease free survival (DFS), with acceptable transplant related mortality (TRM) and with significantly lower relapse rate. Objective: To analyse retrospectively the outcome of relapsed follicular lymphoma patients who received BCNU (carmustine), cytarabine, etoposide, melphalan-alemtuzumab allogeneic HSCT (BEAM-C allo) or BEAM-autologous HSCT (BEAM-auto). Results: The study includes 74 consecutive patients with relapsed advanced stage follicular lymphoma who received BEAM-C allo (n=38) and BEAM-auto (n=36) between 1992 and 2010. Patients characteristics are summarized in Table 1. Median follow-up of surviving patients was 6.1 years. Patients undergoing allo transplants were younger than those who unbderwent and autologous procedure (50 vs 54 years, p=0.018). 1y and 5y TRM was higher in the allo transplant group (27% and 27% vs 6% and 6%; p=0,011). The Cumulative incidence of relapse (CIR) was lower in the allo at 1, 2 and 5 years (11%, 14% and 18% vs 28%, 49% and 60%, p=0,000). Significant differences were not observed in 1, 2 and 5 years OS between allo and auto transplant groups (74%, 74% and 69% vs 85%, 69% and 51%; p=0,217), but we found a strong trend in DFS difference between both groups at 1, 2 and 5 years (65%, 61% and 58% vs 69%, 43% and 33%; p=0.089) observing a plateau around 60% after 2 years in the allograft group. The rate of graft versus host disease (GvHD) was low with 14% acute GvHD (2.6% grade 3–4 GvHD) and 28% chronic GvHD (10% of extensive chronic GvHD). Analysis of the whole cohort (n=74) showed that patients in CR before transplant (n=28) had better 1, 2 and 5 years DFS following a allotransplant (69%, 69% and 69% vs 79%, 36% and 18%; p=0.012). These differences did not affect the 1, 2 and 5 years OS (76%, 76% and 76% vs 93%, 76% and 56%; p=0,214). TRM for the allo transplant group was 24% and 0% R in the auto (p=0,064) in patients when achieved CR before transplant. There were no difference in OS (p=0,785) and DFS (p=0,954) between allo or auto patients in partial response (PR) before transplant. A subgroup analysis of patients with high grade transformation before transplant did not show any differences in OS (p=0,823) or EFS (p=0,526).between allo and auto groups. Conclusions: Long term follow-up of Follicular Lymphoma patients has shown a continuous pattern of relapse when patients receive an autologous transplant, after 5 years. whereas patients undergoing allo transplant, despite a higher mortality, have a 5 year OS and DFS of 60% with a plateau been achieved in both curves after 2 years suggesting that these patients may be cured. Prospective randomised studies are still required to answer the the role of these two approaches in follicular Lymphoma. Disclosures: No relevant conflicts of interest to declare.

Improved Outcome of Allogeneic Transplantation in High-Risk Multiple Myeloma Patients After Nonmyeloablative Conditioning

2002 ◽  
Vol 20 (5) ◽  
pp. 1295-1303 ◽  
Author(s):  
Ashraf Badros ◽  
Bart Barlogie ◽  
Eric Siegel ◽  
Michele Cottler-Fox ◽  
Maurizio Zangari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Residual Disease ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
High Risk Disease ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
N 93

PURPOSE: We present our experience with relapsed and recently diagnosed patients with high-risk multiple myeloma (MM) receiving immunosuppressive, nonmyeloablative melphalan (MEL)-based conditioning regimens (mini-allograft). PATIENTS AND METHODS: Thirty-one MM patients received allografts from HLA-matched siblings (n = 25) or unrelated donors (n = 6) using a mini-allograft. Seventeen had progressive disease (PD) and 14 had responsive disease (RD) (six with primary RD and eight with responsive relapse). Thirty patients had received one (n = 13) or two or more (n = 17) prior autologous transplantations (ATs). Median age was 56 years (range, 38 to 69 years). Twenty-one patients had chromosome 13 abnormality. Two patients were hemodialysis dependent. Blood and bone marrow grafts were administered to 28 and three patients, respectively. Donor lymphocyte infusions were given to 18 patients either to attain full donor chimerism (n = 6) or to eradicate residual disease (n = 12). RESULTS: By day 100, 25 (89%) of 28 patients were full donor chimeras, one was a mixed chimera, and two had autologous reconstitution. Acute graft-versus-host disease (GVHD) developed in 18 patients (58%), and 10 progressed to chronic GVHD (limited in six and extensive in four). At a median follow-up of 6 months, 19 (61%) of 31 patients achieved complete/near complete remission. Twelve patients (39%) have died: three of PD, three of early treatment-related mortality (TRM) (before day 100), and six of late TRM. Median overall survival (OS) was 15 months. At 1 year, there was a significantly longer event-free survival (86% v 31%, P = .01) and OS (86% v 48%, P = .04) when a mini-allograft was performed after one versus two or more prior ATs, respectively. When compared with historical MM controls (n = 93) receiving conventional allografts, early TRM was significantly lower (10% v 29%, P = .03), and OS at 1 year was better (71% v 45%; P = .08) in the mini-allograft MM patients. CONCLUSION: Mini-allograft induced excellent disease control in MM patients with high-risk disease, but is still associated with a significant GVHD.

Non-Myeloablative Allogeneic Transplantation in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2759-2759
Author(s):  
Sabine Gerull ◽  
Ute Hegenbart ◽  
Martin Goerner ◽  
Axel Benner ◽  
Thomas Moehler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Number Of Cycles

Abstract Patients with recurrent and refractory multiple myeloma have a very limited survival expectance. Allogeneic transplantation might offer an option for cure in myeloma and the recent development of non-myeloablative conditioning regimens has reduced transplant related morbidity and mortality and rendered this treatment feasible in elderly patients. The role of non-myeloablative allogeneic transplantation for multiple myeloma however, has not yet been defined. We have analyzed the results of patients with relapsed or refractory multiple myeloma treated at our institution. Between 08/1999 and 02/2004, 56 patients with relapsed (n=54) or refractory (n=2) myeloma were treated with non-myeloablative allogeneic transplantation. The median beta2microglobulin at the time of diagnosis was 2.75 mg/l, and median age at the time of transplant was 54.5 years (39.2–67.8). The median time from diagnosis to transplant was 3.6 years. Prior to allogeneic transplantation, patients received reinduction chemotherapy which included an autologous transplantation for 30 patients. The median number of previous cycles of conventional chemotherapy was 9. The conditioning regimen was 2 Gy TBI with (n=43) or without (n=3) fludarabin 3 x 30 mg/m² for 46 patients, the remaining 10 patients received a melphalan containing regimen. Acute toxicity was low with a WBC < 500/μl and platelets < 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved > 90 % donor chimerism by day 56. Acute GvHD Grade II-IV occurred in 36 % of patients with 22 % Grade III-IV, and 61 % experienced chronic GvHD. Total transplant related mortality reached 20 %, with a day 100 TRM of 5 %. 32 patients experienced relapse or progressive disease, and 32 % of patients died due to relapse. The Kaplan-Meier estimate of overall survival and progression free survival at 18 months was 40 % and 25 %, respectively, with a median follow up of survivors of 21 months. Patients who experienced cGvHD had a significantly higher overall survival estimate (60 % vs. 20 % at 18 months, p=0.03). The number of cycles of pretreatment before allogeneic transplantation had a statistically significant negative influence on overall (p=0.02) and progression free survival (p=0.006). We conclude that non-myeloablative allogeneic transplantation is feasible in patients with relapsed multiple myeloma. The significant poor prognostic factors we identified were absence of chronic GvHD and number of cycles of pretreatment. Allogeneic transplantion should therefore be considered as an option earlier in the course of the disease.

Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3329-3329
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Daniel Couriel ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Albumin Level ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Common Causes

Abstract Background: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually relapse. The optimal salvage treatment for these patients is not very well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage. We analyzed the outcomes of second autologous or allogeneic transplants, performed as salvage in patients relapsing after an autograft. Methods: Fourteen patients received a second autograft for salvage, while thirty-four patients underwent allogeneic transplantation (related 24, unrelated 10). The median age at transplant was 52 years in the autologous group, and 51 years in the allogeneic group. The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The disease characteristics were similar in both autologous and allogeneic groups. Results: With a median follow-up of 10 months among survivors in each group, both autologous and allogeneic transplant groups had a response rate (complete + partial) of 64%. One hundred day nonrelapse mortality was 7% in the autologous group and 12% in the allogeneic group. Median disease-free survival (DFS) was 11 months in the autologous and 6 months in the allogeneic group. Median overall survival (OS) was 29 moths in the autologous and 14 months in the allogeneic group. 1-year DFS was 40% in the autologous group and 22% in the allogeneic group (p = 0.2). 1-year overall survival was 70% in the autologous and 53% in the allogeneic group (p = 0.3). The most common causes of non-relapse mortality were graft vs. host disease (62%) in the allogeneic group, and infections (100%) in the autologous group. On univariate analysis for DFS in allogeneic group, an interval of >1 year between the first and the salvage transplant was the only factor associated with a significantly better outcome (p = 0.01). Disease status at transplant, type of donor, tumor mass, β2 microglobulin level, and serum albumin level did not show any impact on the outcome. Conclusions: Both autografting and allografting are feasible as salvage for myeloma patients relapsing after the first autograft. A slightly better outcome with salvage autografting may be due to decreased toxicity.

Durable Remission with Salvage Autotransplants in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1227-1227
Author(s):  
Nina Shah ◽  
Khawaja Fraz Ahmed ◽  
Sofia Qureshi ◽  
Jatin Shah ◽  
Robert Z Orlowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Time ◽  
Chromosomal Abnormalities ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Remission Duration

Abstract Abstract 1227 Poster Board I-249 Background In comparison with single autologous hematopoietic stem cell transplantation (auto HCT), tandem autologous HCT has resulted in longer event-free and overall survival in randomized trials for patients with newly diagnosed multiple myeloma (MM). Most myeloma patients, however, only receive a single auto HCT. Many of these patients are eligible for a second auto HCT as salvage at the time of relapse. We evaluated the outcome of salvage auto HCT for MM patients treated at our institution. Methods We performed a retrospective chart review and identified 62 MM patients (38 males, 24 females) who received a second auto HCT as salvage between 1/3/1992 and 11/4/2008.. Preparative regimen was high-dose melphalan alone or in combination with other chemotherapy agents, including busulfan, topotecan and bortezomib. Three patients received a combination of thiotepa, busulfan and cyclophosphamide. Results Median interval between the first and salvage auto HCT was 21 months (range 2-81). Median age at salvage HCT was 55 years (37-73) and median prior treatment regimens were 4 (range 2-16). Twelve patients had chromosomal abnormalities on conventional cytogenetic studies. Patients received a median CD34 cell dose of 4 ×106 / kg (range 2.3-11.2). Fourteen patients (22%) experienced grade 3 or higher toxicity after the salvage auto HCT. Two patients died within 100 days with a TRM of 3%. Median time to neutrophil engraftment was 10 days (8-38). Responses after salvage auto HCT were as follows: CR+ near CR 15%, PR 48%, with an overall response rate of 63%. Twenty-seven (44%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 25 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) were 15.5 and 43.3 months, respectively. Median time to progression after the first and salvage auto HCT was 20 and 12 months, respectively, with total remission duration of 32 months from two HCTs. Median OS from the time of diagnosis was 72 months, comparable to reported results with tandem auto HCT. At last follow up, 20 patients were alive and in remission. Conclusions In selected MM patients a second auto HCT for salvage therapy is well tolerated with acceptable toxicity. The combined remission duration and overall survival are comparable to outcomes with tandem autotransplants. Disclosures Qazilbash: Cephalon: Speakers Bureau.

Long Term Outcome After Low Dose TBI Based Conditioning Hematopoietic Stem Cell Transplantation (HSCT) From Related and Unrelated Donors for Older Patients with AML

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2030-2030
Author(s):  
Dietger Niederwieser ◽  
Leo F Verdonck ◽  
Jan J Cornelissen ◽  
Michael Cross ◽  
Rainer Krahl ◽  
...  
Keyword(s):  
De Novo ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Study Groups ◽  
Long Term Results ◽  
Term Outcome ◽  
Hematopoietic Stem ◽  
Long Term Outcome

Abstract Abstract 2030 HSCT after reduced or minimal intensity conditioning is increasingly used to treat AML patients not eligible for conventional HSCT. Short term outcome has been reported frequently and risk factors have been identified; long term results still await in depth evaluation. We report here 5 years follow up results from a prospective phase II study conducted by two AML study groups in Europe. Patients were recruited from AML protocols HOVON/SAKK AML 43 and the OSHO AML 1997 study. The regimen consisted of fludarabine (FLU), 30 mg/m2/d on days −4, −3, and −2, 2 Gy TBI on day 0 (the day of HSCT) with mycophenolate mofetil, [15 mg/kg p.o. b.i.d. from 5 hours after HSCT to day +40], and cyclosporine, [CSP; 6.25 mg/kg p.o. bid from day –3 to day +180] after HSCT. Cyclosporine was adjusted to trough levels and reduced according to a predetermined tapering schedule and donor type. A total of 96 patients were recruited between 5/2002 and 8/2005 in the study. Age was median 62 (range 40 – 74) years, 54 patients were male (56%) and 73 patients (76%) had de novo AML. The remission status on entry was CR1 in 83 (86%) patients and CR2 in 13 (14%). Of the 96 patients, 20% had high risk cytogenetics and SCT was performed a median of 75 days after chemotherapy. There were no statistical differences in the above described characteristics except for more secondary AML (p=0.04) and more CR2 patients (p=0.07) among the 59 unrelated SCT (61%) as compared to the 37 related SCT (39%). Graft rejection at two years was observed in 6% of the patients. Absence of chronic GvHD was diagnosed in 40% and limited chronic GvHD in 29% of the patients, with no difference between related and unrelated SCT. Probability of overall survival (OS) at 6 years with a median follow up of 64 (49–92) months reaches a plateau after 5 years at 0.33±0.05 and was not significantly better in CR1 than in CR2. However, there was a trend towards better OS at 6 years for unrelated 0.41±0.11 as compared to related 0.29±0.07 SCT (p=0.08) in CR1 only. This difference was significant for disease free survival (DFS) (0.48±0.09 unrelated vs 0.27±0.06 related; p=0.04), the major reason being a higher relapse rate in related as compared to unrelated SCT (0.62±0.08 vs 0.40±0.09). The overall non-relapse mortality at 6 years was 0.21±0.05. We conclude that OS and DFS reach a stable plateau from 5 years after SCT to more than 8 years after SCT. In CR1 patients, DFS is superior after unrelated as compared to related SCT. Accordingly, strategies designed to decrease relapse, especially after related SCT, have already been implemented in the ongoing protocols. The preferential use of unrelated rather than related donors may be beneficial and should be considered in future protocols. Disclosures: Off Label Use: Transplantation in elderly patients.

Lenalidomide Maintenance Therapy After Toxicity-Reduced Myeloablative Allograft As Salvage Therapy for Efractory/Relapsed Myeloma Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3024-3024
Author(s):  
Nicolaus Kröger ◽  
Evgeny Klyuchnikov ◽  
Thomas Stübig ◽  
Christine Wolschke ◽  
Francis Ayuk ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Graft Versus Host Disease ◽  
Cumulative Incidence ◽  
Myeloablative Conditioning ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Iii

Abstract Abstract 3024FN2 Reduced-intensity conditioning (RIC) regimen followed by allogeneic stem cell transplantation (SCT) has become a reasonable treatment option for patients with multiple myeloma who are refractory or have relapse to an autograft. However, in comparison to standard myeloablative conditioning RIC resulted in higher risk of relapse. Maintenance therapy after autologous transplantation has shown to improve survival while after allogeneic SCT data are lacking so far. We here report the results of myeloablative toxicity-reduced allograft consisting of intravenous busulfan (12.2 mg/kg) and cyclophosphamide (120 mg/kg) followed by lenalidomide maintenance in 33 patients with multiple myeloma who relapsed to an autograft. A total of 32 patients had received one (n=16), two (n=15), or even three (n=1) autografts, and 1 patient was refractory to 2 induction therapies and failed to collect autologous stem cells. The median duration of remission after the autograft was 12 months. The primary endpoint of the study was non-relapse mortality at 1 year and secondary objectives were evaluation of response, incidence of acute and chronic graft-versus-host disease as well as progression and overall survival. To prevent graft-versus-host disease antithymocyte globulin (ATG Fresenius®) was given at a median dose of 20 mg/kg on day -3, -2, and -1. Lenalidomide was started earliest at day 120 after transplantation if there were no signs of infection or graft-versus-host disease. The median time between last autograft and allogeneic transplantation was 20 months. 19 patients were treated with fully HLA-matched unrelated donor, 8 patients had a mismatch donor, and 6 patients were transplanted from an HLA-identical sibling. 2 patients died of treatment-related complications resulting in a cumulative incidence of non-relapse mortality at 1 year of 6% (95% CI: 0–14%). After transplantation 27% developed grade II graft-versus-host disease, and severe grade III graft-versus-host disease was seen in 6% of the patients. Complete remission was noted in 46% of the patients, partial remission was seen in 48% and stable disease in 3%. The median interval between allogeneic transplant and start of lenalidomide was 168 days. The median starting dose was 5 mg (range 5–15 mg) without dexamethasone for 21 day followed by 1 week rest. 9 patients did not receive lenalidomide maintenance due to ongoing graft-versus-host disease, cytopenia or patient's wish. The median number of lenalidomide cycles was 6 (range 1–30). During follow-up 13 patients discontinued lenalidomide treatment due to progressive disease (n=6), GvHD (n=3), thrombocytopenia (n=2), or fatigue (n=2). In 10 patients lenalidomide dose could be increased to 10 or 15 mg, respectively. The major toxicities of lenalidomide were acute graft-versus-host disease grade I – III (21%), viral reactivation (12%), thrombocytopenia grade III-IV (12%), neutropenia grade III-IV (6%), peripheral neuropathy grade I-II (12%), or other infectious complications (6%). During follow-up 9 patients experienced relapse resulting in a cumulative incidence of relapse at 3 years of 42% (95% CI: 18–66%). The 3 year estimated probability of progression-free and overall survival was 52 % (95% CI: 28–76%) and 79 % (95% CI: 63–95%), respectively. In the current trial neither the deletion 13q14 nor the use of mismatch donor nor the chemosensitivity prior allogeneic SCT could be identified as risk factor for survival. This study showed that toxicity-reduced myeloablative conditioning regimen is feasible and highly effective in relapsed patients with multiple myeloma resulting in an acceptable treatment-related mortality. Lenalidomide as maintenance therapy is feasible early after transplantation but toxicity especially the induction of graft-versus-host disease should be considered. Disclosures: Kröger: Celgene: Research Funding. Kropff:Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

Comparison of Autologous and Allogeneic Transplantation As Therapy of First Relapse in Patients with Multiple Myeloma - Long-Term Follow up Analysis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4124-4124
Author(s):  
Ute Hegenbart ◽  
Stefan O Schonland ◽  
Axel Benner ◽  
Christina Wunder ◽  
Thomas M. Moehler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Chronic Gvhd ◽  
High Dose ◽  
Two Stage ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
First Relapse ◽  
First Diagnosis

Abstract Abstract 4124 BACKGROUND: Most patients (pts) undergoing high-dose therapy with melphalan 200 mg/m2 (HDM) and autologous transplant for multiple myeloma (MM) develop disease recurrence. The optimal salvage treatment including autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (SCT) as consolidation therapy for these patients is not yet defined. METHODS: We performed a retrospective analysis of 116 pts with MM treated in our institution between 1999 and 2005. Inclusion criteria were relapse after auto-SCT (n=88) or failure of induction treatment (n=28) and age ≤ 65 years. Re-induction was performed with TCED (thalidomide, cyclophosphamide, etoposide and dexamethasone (Möhler et al, Blood 2001). Seventy-one pts (median age, 59 yrs) received auto-SCT (auto-group) after HDM followed by maintenance therapy with thalidomide or interferon-alpha in 42 pts. Forty-five pts (allo-group, median age, 53 yrs) underwent a reduced-intensity allo-SCT (related in 24 pts), mostly using conditioning with 2 Gy total body irradiation and fludarabine. Thirty-eight pts received an auto-allo-tandem-SCT (Maloney, Blood 2003) and 7 pts have been directly transplanted after TCED. Statistical analysis was done using the two-stage test of Qiu & Sheng (JRSS Ser. B 2008) to compare two possibly crossing survival curves. Extended Cox proportional hazards regression models were applied to allow for time-varying differences between the two SCT groups. RESULTS: Estimated median follow-up after start of TCED was 95 months. All pts received a median number of 3 TCED cycles for re-induction therapy. 64 of 116 pts (55%) showed at least a PR after TCED chemotherapy (CR in 3 pts). TRM was 17% after 2 years in the allo-group and differed significantly from the auto-group (3%, p=0.02). More CR were achieved after allo-SCT compared to auto-SCT (17 vs. 4 pts., p<0.001). Median overall survival (OS) was 26 months for the auto group and 23 months for the allo group (Figure 1, p=0.16). Median progression-free survival (PFS) was 12 months for both groups but crossing hazards were observed (Figure 2, p=0.03, two-stage test of Qiu & Sheng). The results of multivariate regression analysis for OS and PFS including age at relapse-SCT, response to TCED, time between first diagnosis until first relapse-SCT and primary progression are shown in table 1. In the allo group, there was no OS or PFS difference between related and unrelated donors (multivariate analysis). Cumulative incidence of chronic GvHD was 73% (53% extensive). Patients with chronic GvHD showed a better OS and PFS than pts without (univariate analysis, both p<0.01). CONCLUSIONS: To our knowledge, this is the first analysis in a large number of patients with a long follow-up comparing allo with auto SCT in 1st myeloma relapse which were treated uniformly with TCED therapy for re-induction. Main problem was MM recurrence. However, younger pts with disease response after TCED and longer time from first diagnosis to first SCT after relapse profit best from TCED and this transplant approach. Most interestingly, disease control is better after allo compared to auto SCT in univariate and multivariate analysis leading to a PFS of about 20% after 4 years. In our opinion, allo SCT is a valuable clinical option for patients with 1st relapse after HDM and auto SCT. Disclosures: No relevant conflicts of interest to declare.

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