Intravenous Busulfan (IV Bu)-Based Conditioning Regimen Before Allogeneic Stem Cell Transplantation (allo-SCT) for Adults with Acute Lymphoid Leukemia (ALL): A Aurvey From the Acute Leukemia Working Party of EBMT

Abstract Abstract 3005 Allo-SCT is an effective postremission therapy when compared to chemotherapy for adult patients with ALL. However, some studies suggested that the benefits from allo-SCT antileukemia effects are offset from the high non-relapse mortality (NRM), especially when using high dose TBI-based myeloablative conditioning. At present, it is well established that IV BU is as potent in inducing apoptosis of primary ALL cells as it is in AML. Marrow ablative or nonmyeloablative doses of IV BU were shown to be well tolerated in older adults when used as part of the conditioning regimen. With this background, this survey performed between 2000 and 2010, aimed to assess the outcome of 467 adult patients with ALL who received IV Bu-based conditioning regimen (without TBI) prior to allo-SCT. In this series, the median age was 37 years (range, 18–71) and the median year of allo-SCT was 2008. A B-lineage ALL was diagnosed in 317 cases (68%). 274 patients (59%) received allo-SCT from an HLA-matched related donor, while 168 patients (36%) received an HLA-matched unrelated graft (at least 6/6 match), and 25 (5%) received an HLA-mismatched graft. G-CSF-mobilized PBSCs were used as stem cell source in 387 cases (83%), and bone marrow in the remaining 80 cases (17%). At time of allo-SCT, 301 patients (64%) were in first CR, 88 patients (19%) in second CR and 78 cases (17%) in more advanced phases. As per inclusion criteria, all patients from this series received a conditioning regimen combining IV Bu and other chemotherapeutic drugs. 359 patients (77%) received a standard myeloablative conditioning (MAC) regimen (252 cases consisting of IV Bu 3.2 mg/Kg/day for 4 days and Cy; 77 cases IV Bu and Fludarabine, and 30 cases of IV Bu and other drugs). The remaining patients (23%) received a so-called reduced-intensity conditioning (RIC) consisting of nonmyeloablative doses of IV Bu (total dose ≤ 9.6 mg/Kg) and Fludarabine in the majority of cases (89%). In this series, 96% of patients achieved neutrophil engraftment at a median time of 15 days after allo-SCT. The incidences of grade II and grade III-IV acute GVHD were 18% and 10%, respectively. When considering patients in first CR who received transplant from an HLA-identical sibling, the cumulative incidence of NRM was 14±3% at 2 years. NRM was 29±8% at 2 years in patients transplanted in second CR from an HLA-identical sibling. In the unrelated transplant group, NRM incidences were 31±6% at 2 years for patients transplanted in first CR and 41±8% for patients transplanted in second CR. The cumulative incidences of relapse were 38±4% at 2 years for patients transplanted in first CR and 41±7% for patients transplanted in second CR using a matched related donor. In the unrelated transplant group, relapse rates were 31±5% at 2 years for patients transplanted in first CR and 44±8% for patients transplanted in second CR. With a median follow-up of 12 months (range, 1–88) after allo-SCT, leukemia-free survival (LFS) was 48±5% at 2 years for patients transplanted in first CR using an HLA-identical sibling. LFS was 30±8% at 2 years for patients transplanted in second CR using an HLA-identical sibling. In the unrelated transplant group, LFS rates were 38±6% at 2 years for patients transplanted in first CR and 15±6% for patients transplanted in second CR. In summary, results from this survey suggest that the use of IV Bu-based conditioning regimen may represent a valid option for the conditioning of adult ALL patients prior to allo-SCT. The use of IV-Bu-based RIC allowed a significant number of ALL patients not eligible to MAC to proceed to allo-SCT. Outcomes (NRM, LFS and relapse incidence) achieved after such regimens (especially in patients in first CR) compare favourably to figures from historical series using TBI-based conditioning, warranting a prospective randomized trial. Disclosures: Mohty: Pierre Fabre: Consultancy, Honoraria, Speakers Bureau. Nagler:Pierre Fabre: Honoraria.

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Allogeneic Stem Cell Transplantation from Unrelated Donors after Reduced Intensity Conditioning in Patients with MDS/sAML. A Report from the Chronic Leukemia Working Party (CLWP) of the EBMT.

Blood ◽

10.1182/blood.v104.11.5176.5176 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5176-5176 ◽

Cited By ~ 2

Author(s):

Nicolaus Kroeger ◽

Ronald Brand ◽

Rodrigo Martino ◽

Philippe Guardiola ◽

Anja van Biezen ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Disease Free Survival ◽

Working Party ◽

Stem Cell Source ◽

Unrelated Donors

Abstract We analysed the results of 67 patients with MDS/sAML who were transplanted with allogeneic stem cell transplantation from unrelated donors after a reduced intenisity conditioning and reported to the EBMT. The median age was 52 years (range 17–70 years) and stem cell source was bone marrow (n = 30) or peripheral blood progenitor cells (n = 33).. The graft was HLA matched in 57 patients while 8 patients received SCT from HLA-mismatched donor. The MDS classification was as follows: RA/RARS: n=8, RAEB/CMML: n = 14, RAEB-t/sAML: n = 22. The conditioning regimen consisted of fludarabine/busulfan (n=15), fludarabine/melphalan (n=6), fludarabine and TBI (n=8) or fludarabine and others (n=36)At time of transplantation only 12 (18%) were in first complete remission. The Kaplan-Meier estimates of the probability of 2 years overall and disease free survival were 33 % (95% CI: 21–45 %) and 24 % (95% CI: 12–36 %), respectively. The probability of relapse at two years was 58 % (95% CI: 40–76 %) and of one year treatment-related mortality 37 % (95% CI %: 23–51 %). In an univariate analysis assessing source of stem cells, age, disease type, T-cell depletion, and HLA-matching no factor was significant for OS, EFS, TRM and Relapse. Allogeneic stem cell transplantation after a reduced intensified conditioning followed by unrelated SCT seems to be a feasible approach in those patients who were no candidates for a standard conditioning but is associated with a considerable number of relapses.

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Allogeneic Hematopoietic Stem-Cell Transplantation Using Fludarabine/Treosulfan Conditioning Regimen Compared with Busulfan-Based Myeloablative and Reduced-Intensity Conditioning in Patients with AML and Mds; Relative Outcomes Depend On Disease Status at Transplantation.

Blood ◽

10.1182/blood.v114.22.3358.3358 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3358-3358

Author(s):

Avichai Shimoni ◽

Avital Rand ◽

Noga Shem-Tov ◽

Izhar Hardan ◽

Yulia Volchek ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Conditioning Regimen ◽

Dose Intensity ◽

High Dose ◽

Reduced Intensity Conditioning ◽

Myeloablative Conditioning ◽

Adverse Factor ◽

Active Disease ◽

Reduced Intensity

Abstract Abstract 3358 Poster Board III-246 Allogeneic stem-cell transplantation (SCT) with both myeloablative (MAC) and reduced-intensity conditioning (RIC) is effective therapy in AML and MDS. However, the relative merits of each may differ in different settings. We have previously reported on the role of dose intensity in a group of 112 patients (pts) with AML/MDS given allogeneic SCT with different busulfan (Bu)- based regimens (Leukemia 2006). We showed that survival was similar with MAC and RIC in pts given SCT in remission, but was inferior in pts given RIC in active disease due to high post transplant relapse rates. The combination of fludarabine and treosulfan (FT) has been reported as an effective regimen in AML/MDS with limited toxicity. However, the relative dose intensity and expected outcomes with FT in the different SCT settings, compared with Bu-based regimens is not well defined. We now extend the analysis to a group of 298 pts with AML/MDS, given allogneic SCT from sibling (n=153) or unrelated/mismatched donors (n=145) and included the more recently introduced FT regimen. Pts meeting standard eligibility criteria for myeloablative conditioning were given high dose iv Bu and cyclophosphamide (BuCy, n=81). Pts with a risk factor for MAC, mainly due to advanced age, were given fludarabine (F) and reduced doses of Bu (6.4 mg/kg, FB2, n=91), F with high dose Bu (12.8 mg/kg, FB4,n=63) or FT (treosulfan 30-36 gr/m2). Protocol allocation was not randomized, resulting in a younger age for pts in the BuCy group; median age 37 years compared with 60, 50, and 58 for FB2, FB4 and FT, respectively. BuCy and FT groups included more pts with active disease at SCT, while the BuCy group had less unrelated donors. Non-relapse mortality (NRM) was 17%,18%,18% and 20% with FB2,FB4,FT and BuCy, respectively (p=NS). However, pts were selected to regimens other than BuCy based on a high estimated risk for NRM. With a median follow-up of 38 months (range, 1-115), estimated 5-yr overall survival (OS) was 38% (95%CI, 31-44). OS rates were 36%,33%,43% and 41% after FB2, FB4, FT and BuCy, respectively (p=NS). Multivariate analysis (MVA) defined age>50 [HR 1.5 (1-2.2), p=0.05)], active disease at SCT [HR 2.3 (1.6-3.2), p<0.001)] and unrelated donor [HR 1.5 (1-2.0), p=0.02)], as risk factors for shorter OS. The conditioning regimen used was not predictive in the entire group. When the analysis was limited to pts in first or subsequent remission (n=126), OS was 51%,43%,58%, and 43%, respectively. MVA identified age>50 as an adverse factor, while SCT using FB2 or FT was associated with prolonged OS [HR 0.3 (0.2-0.7), p=0.002)]. When the analysis was limited to pts with active disease (n=172) either chemo-refractory to induction or subsequent therapy (n=93) or untreated [n=79; untreated relapsed AML (n=15) or MDS with excess of blasts (n=64)], OS was 12%,25%,32%, and 36%, respectively. MVA identified chemo-refractory disease as the major adverse factor; OS [HR 2.2 (1.5-3.3), p=0.001), while SCT using BuCy or FT was associated with prolonged OS [HR 0.7 (0.5-1.0), p=0.06)]. The advantage of FT was observed mainly in pts with active untreated disease (mostly MDS). OS was 57% (95%CI, 32-82) in a group of 25 pts given FT for advanced, previously untreated MDS. Only BuCy and to a lesser degree FB4 (OS 27%) were effective in the truly refractory pts. FB2 and FT, were associated with a grim outcome in this setting (OS 6%, p=0.04). In conclusion, dose intensity is associated with different outcomes in the different transplant setting. In pts in remission at SCT, outcome is mostly related to SCT toxicity, thus there is an advantage to less intensive regimens, such as FB2, while FT shares this characteristic. When outcome is dominated by the risk for relapse, such as in pts with active disease at SCT, there is an advantage to a more intensive regimen, such as BuCy. FT shares this characteristic mainly in pts with no true chemo-refractoriness, and has an advantage over FB2 in this setting. FT should be considered as a reduced toxicity myeloablative conditioning, that is feasible in pts ineligible for MAC, rather than a reduced-intensity regimen. In pts in CR toxicity is comparable to FB2 while in pts with active untreated MDS its anti leukemic activity is comparable to BuCy. Disclosures: No relevant conflicts of interest to declare.

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Reduced Intensity Versus Conventional Myeloablative Conditioning (RIC vs. MAC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Lymphoblastic Leukemia (ALL): A Survey from the Acute Leukemia Working Party of EBMT

Blood ◽

10.1182/blood.v112.11.793.793 ◽

2008 ◽

Vol 112 (11) ◽

pp. 793-793 ◽

Cited By ~ 2

Author(s):

Mohamad Mohty ◽

Myriam Labopin ◽

Tapani Ruutu ◽

Alois Gratwohl ◽

Gerard Socie ◽

...

Keyword(s):

Stem Cell ◽

Cumulative Incidence ◽

Negative Impact ◽

Therapeutic Option ◽

Lymphoblastic Leukemia ◽

Working Party ◽

High Dose ◽

Adult Age ◽

Stem Cell Source ◽

Significant Difference

Abstract The exact role of RIC allo-SCT for adult patients with ALL is still under considerable debate. While the use of such so-called nonmyeloablative or RIC regimens has emerged as an attractive modality to decrease transplant-related mortality, toxicity might represent only one aspect of the problem, since ALL encompasses a group of chemosensitive diseases, raising concerns that significant reduction of the intensity of the preparative regimen may have a negative impact on long-term leukemic control. In this multicenter retrospective study, the outcomes of 601 adult (age at transplantation >45 y.) patients with ALL who underwent transplantation in complete remission (CR) with an HLA–identical sibling donor, were analyzed according to 2 types of conditioning: RIC in 97 patients, and standard MAC (or high-dose) in 504 patients. Both groups were comparable in terms of gender, CR status (CR1 and CR2), interval from diagnosis to allo-SCT, and recipient/donor CMV serostatus. Patients in the RIC groups were older (median 56 y. vs. 50y in the MAC group; P<0.0001), Most of the patients in the MAC group received high dose TBI (80%), while the majority of the RIC regimens included either low-dose TBI or were ATG+chemotherapy-based regimens. The majority of patients (88%) from the RIC group received a PBSC graft. In the MAC group, the stem cell source consisted of bone marrow in 42% of patients. With a median follow-up of 13 months (range, 1–127), the incidences of grade II-IV and grade III-IV acute GVHD were: 35%, 14%, and 28%, 10% in the MAC and RIC groups respectively (P=NS). The cumulative incidence of non-relapse mortality at 2 years (NRM) was 32% (MAC) vs. 22% (RIC) (P=0.04). The cumulative incidence of relapse at 2 years was 30% (MAC) vs. 42% (RIC) (P=0.0007). However, the latter differences did not translate into any significant difference in term of leukemia-free survival (LFS) at 2 years: 38% (MAC) vs. 37% (RIC) (P=0.42). In multivariate analysis for LFS, the status at transplant was the only factor associated with an improved LFS (p<0.0001, RR=0.55, 95%CI, 0.42–0.72). The results of this retrospective registry based study suggest that RIC regimens may reduce NRM rate after allo-SCT for adult ALL when compared to standard MAC regimens, but with a higher risk of disease relapse and no impact on LFS. The latter represent promising findings, since patients who received RIC are likely to have serious comorbidities, which led the transplantation center to choose RIC, and surely most of these patients would not have received a standard allo-SCT in most institutions. Therefore, RIC allo-SCT for adult ALL (>45 y.) may represent a valid therapeutic option when a conventional standard conditioning is not possible, warranting further prospective investigations.

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Haploidentical Peripheral Blood Stem Cell Transplantation Using Non-Myeloablative Conditioning With Post-Transplant Cyclophosphamide Regimen Is Safe and Is Associated With Very Encouraging Post-Transplant Outcomes

Blood ◽

10.1182/blood.v122.21.4532.4532 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4532-4532

Author(s):

Pavan Kumar Bhamidipati ◽

John F. DiPersio ◽

Keith Stokerl-Goldstein ◽

Geoffrey L. Uy ◽

Peter Westervelt ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

T Cell ◽

Conditioning Regimen ◽

High Dose ◽

Unrelated Donor ◽

Myeloablative Conditioning ◽

Free Survival ◽

Post Transplant ◽

Cell Sources

Introduction The availability of HLA matched donors remains a major obstacle for successful allogeneic hematotopoietic cell transplantation. The use of HLA-mismatched alternate donors such as cord blood and haploidentical donor stem cell sources have allowed for greater access for those patients who need an allo-HSCT but lack a suitable matched sibling or unrelated donor. Introduction of high dose cytoxan in the early post-transplant period has significantly improved the outcomes of patients undergoing haploidentical transplantation and has eliminated the need for expensive and labor-intensive ex-vivo T cell depletion. Encouraging results have been reported using this platform with bone marrow as the source of stem cells. However, there have been only limited reports using this transplant platform with G-CSF mobilized peripheral blood stem cells (PBSC) as a source of stem cells for haloidentical transplantation. Here we report the outcomes of 18 patients who underwent haploidentical transplant for hematological malignancies from single institution treated on the Hopkins non-meloablative conditioning regimen but with G-CSF mobilized PBSC as a source of stem cells from a haplo-identical family donor. Patients and Methods A total of 18 patients (median age 41 years, range 22-73 years, 11 males and 7 females) between July 2009 and June 2013 underwent haploidentical transplant at Washington University School of Medicine in St Louis using the Hopkins non-myeloablative conditioning regimen with post transplant cytoxan (fludarabine (30 mg/m2/day on days -6 to -2), cytoxan (14.5 mg/kg/day on days -6 and -5) and TBI (single dose at 200cGy on day -1) and all these patients received two doses of post-transplant cytoxan (50mg/kg on D+3 and D+4). G-CSF mobilized PBSC from parents (n=9) or siblings (9) were used as a graft source with median CD34+ cell dose of 5.0 x 106/kg and median CD3+ T cell dose of 19.7 x 107/kg. GVHD prophylaxis regimen included MMF plus tacrolimus (16/18 patients) or MTX plus tacrolimus (2/18 patients). Median follow-up of all patients was 251 (range 17-1174) days. Diagnoses included AML (n=12), ALL (n=2), NHL (n=2), CLL (n=1) and aplastic anemia (n=1). 7 out of 12 AML patients underwent transplant with active disease (not in remission) and 4/18 of these patients had prior history of allogeneic HCT. Results 16 patients (89%) engrafted (> 95% donor chimerism), median time to neutrophil engraftment was 15 days (range: 12-28 days) and median time to platelet engraftment was 18 days (range: 11-40 days). None of these patients had secondary graft failure. 1-year overall survival (OS) for all patients was 62% and 100-day and 1-year non-relapse mortality (NRM) rates were 11% and 17% respectively. Both 1-year and 2-year relapse free survival (RFS) rates were 53%. Despite very high CD3+ T cell doses, cumulative incidence of grade II-IV aGVHD was 40.7% while grade III-IV aGvHD occurred in only 3 patients (17%). Cumulative incidence of cGVHD at 1 and 2 years were both at 8% (extensive in only 1 patient). CMV reactivation occurred in 11 patients (61%) but did not significantly impact their survival or relapse rates and none of these patients developed CMV disease. Conclusions Here we report the outcomes of 18 patients with hematologic malignancies or marrow failure states undergoing haploidentical transplant using the published Hopkins NMA conditioning platform with post-transplant high dose cytoxan and with G-CSF mobilized PBSC as a source of donor stem cells. In spite of the limited numbers of patients transplanted, our results suggest that this approach is both safe and effective and associated with rapid multilineage engraftment, low rates of both aGvHD and cGvHD and encouraging overall and disease-free survival rates and low rates of NRM. Based on these results, 1) G-CSF mobilized PBSC from haploidentical donors should be considered as an alternative source of haploidentical stem cells to BM and 2) future randomized trials using this platform to test the role of haploidential G-CSF mobilized PBSC with other unrelated donor stem cell sources (cord blood and matched unrelated could also be considered in the future. Disclosures: Abboud: Alexion: Honoraria; Ariad: Honoraria; Novartis: Honoraria; Teva: Speakers Bureau.

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Autologous Stem Cell Transplantation (ASCT) for the Treatment of Patients with Waldenstrom’s Macroglobulinemia / Lymphoplasmacytic Lymphoma (WM/LPL). a Risk Factor Analysis By the European Society for Blood and Marrow Transplantation (EBMT) Lymphoma Working Party

Blood ◽

10.1182/blood.v124.21.678.678 ◽

2014 ◽

Vol 124 (21) ◽

pp. 678-678 ◽

Cited By ~ 3

Author(s):

Charalampia Kyriakou ◽

Ariane Boumendil ◽

Herve Finel ◽

Jean-Paul Vernant ◽

Jan J. Cornelissen ◽

...

Keyword(s):

Stem Cell ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Disease Free Survival ◽

Working Party ◽

Disease Status ◽

Female Gender ◽

High Dose ◽

Stem Cell Source ◽

The Impact

Abstract WM/LPL is a rare distinct indolent lymphoma and the optimal management of the disease remains a major challenge. Combination therapies with old and novel agents have markedly improved the response rates and the quality of response but still the CR rates remain low and so far there is no cure. The role and timing of ASCT in the management of patients with WM/LPL has not been well established. The aim of the present study was to investigate the outcome of ASCT in early vs late WM/LPL. Methods: Eligible for this retrospective study were all patients who had a first ASCT for WM/LPL between 1995 and 2011 and were registered with the EBMT database. Baseline patient, disease, and transplant data were collected from MED-A forms. Statistical analysis used log rank tests to assess the impact of baseline characteristics on survival endpoints. Overall survival (OS) and disease-free survival (DFS) was estimated from the time of ASCT using Kaplan-Meier product-limit estimates. Curves of cumulative of non-relapse mortality (NRM) and incidence of relapse (IR) were compared by Gray’s test in a competing risk framework. Results: Altogether 615 patients fulfilling the inclusion criteria were identified in the database. The median age at ASCT was 53 years (range 19-76), and 428 patients (70%) were male. The median time from diagnosis to ASCT was 19 months (interquartile range: 10-51 months). 537 patients (71%) underwent ASCT after 2002. Disease status at ASCT was first partial (PR1), very good partial (VGPR1) or complete remission (CR1) in 325 patients, whilst 176 patients were autografted in second, third or later response, and 47 patients (4%) had primary refractory or progressive disease at ASCT. High-dose therapy was TBI-based in 82 patients (14%), and stem cell source was from peripheral blood in 598 patients (97%). With a median follow-up of surviving patients of 53 months, the 5-year OS was 65%, DFS was 46%, IR was 47% and NRM was 7%. IR was significantly lower in patients receiving ASCT in first response (CR1, VGPR1, PR1) compared to transplantation in subsequent complete or partial responses or with refractory disease (39% vs 53%; p=0.001), translating into a significant DFS (50% vs 40%, p= 0.004) and OS benefit (71% vs 63%; p= 0.033) for the patients transplanted early. DFS was significantly better for patients receiving ASCT after year 2000 compared to the patients transplanted before (p=0.031) and although the year of ASCT had influence on the OS this did not reach statistical significance (p=0.068). Multivariate analysis considering age, sex, disease status at ASCT, and ASCT year confirmed ASCT beyond 1st remission (HR 1.37, 95%CI 1.04-1.79), along with female gender (HR 0.73, 95%CI 0.54-0.97) and ASCT between 2001-2005 (vs before 2001; HR 0.66, 95%CI 0.47-0.92) as significant predictors of DFS. Conclusions: These results suggest that ASCT is a feasible and effective treatment for WM/LPL. Factors predicting for a favourable DFS are female gender, transplantation in the rituximab era, and ASCT in first remission. However, with DFS and OS of 40% and 63% at 5 years, even the outcome of patients undergoing ASCT with advanced disease is still encouraging. As single-hit ASCT can induce long term response with relatively low toxicity and economic burden, it may serve as benchmark for the upcoming novel targeted therapeutics entering the WM / LPL treatment arena. Disclosures No relevant conflicts of interest to declare.

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Bortezomib-Based Induction Therapy Induces Better Responses and Outcomes of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: The Results of Korean Multiple Myeloma Working Party Retrospective Study, KMM84

Blood ◽

10.1182/blood.v112.11.5184.5184 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5184-5184 ◽

Cited By ~ 1

Author(s):

Seok Jin Kim ◽

Kihyun Kim ◽

Jae Hoon Lee ◽

Min Kyoung Kim ◽

Jae-Yong Kwak ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Induction Therapy ◽

Conditioning Regimen ◽

Working Party ◽

Complete Response ◽

High Dose ◽

Significant Difference

Abstract Introduction: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) generally offers improved outcomes compared with conventional chemotherapy in patients with multiple myeloma. The disease status before ASCT such as the achievement of complete response (CR) was also reported as an important prognostic factor in multiple myeloma. Thus, the type and efficacy of induction therapy could affect the treatment outcome of ASCT because these induction chemotherapy regimens are designed to reduce myeloma burden leading to CR before ASCT. A combination chemotherapy regimen, VAD consisting of vincristine, doxorubicin, and dexamethasone is the induction therapy regimen which has been used for a log time. However, many new induction regimens have been used including thalidomide plus dexamethasone, and bortezomib since their efficacy was proven for relapsed or refractory multiple myeloma. However, the efficacy of these new induction therapy regimens and their effects on outcomes of ASCT has rarely been compared to VAD induction therapy. Methods: We performed a retrospective multicenter analysis supported by the Korean Multiple Myeloma Working Party (KMMWP). We have compared the efficacy of induction therapy regimens including VAD chemotherapy, thalidomide-based induction therapy, bortezomib-containing induction therapy, cyclophosphamide-based therapy. We also assessed the effects of these induction therapies on the outcome of ASCT in terms of response, relapse after ASCT, and survival. Results: We analyzed 344 patients who received induction therapy followed by high-dose chemotherapy with single ASCT at 13 hospitals in Korea. Patients who received tandem ASCT or ASCT followed by allogeneic stem cell transplantation were excluded. Their median age at diagnosis was 55 year old (range 20–72). The most common immunophenotype was IgG kappa and lambda (103, and 63 respectively) while 72 patients had light chain disease (kappa 30, lambda 42). 241 patients (70.1%) received VAD chemotherapy as an induction therapy prior to ASCT, and 35 patients (10.2%) received thalidomide-based chemotherapy before ASCT including thalidomide with/without dexamethasone. 46 patients (13.4%) were exposed to bortezomib including bortezomib alone or combined with other agents such as bortezomib, doxorubicin, dexamethasone (PAD). 22 patients (6.4%) received cyclophosphamide-based induction therapy. Age, sex, stage (Durie-Salmon and International staging system), and immunophenotype were balanced among these four groups of patients. Complete response (CR) rate including nCR (near CR) of VAD chemotherapy was 20.3% (49/241). CR rate of bortezomib and thalidomide-based therapy was 43.5% (20/46), and 37.1% (13/35) respectively. Cyclophosphamide-based induction therapy induced 27.2% of CR (6/22). Thus, CR rate of bortezomib-based induction therapy was significantly higher than other regimens (P < 0.05). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. The melphalan-based conditioning regimen was used in all patients, and the dosage of melphalan was from 100mg/m2 to 200mg/m2. There was no difference of conditioning regimen among the four groups. When we assessed the response after ASCT, the results were as follows: VAD group (48 patients with continued CR, 85 patients with induced CR, 55.2% of CR rate), Thalidomide group (20 patients with continued CR, 12 patients with induced CR, 60.0% of CR rate), Bortezomib group (20 patients with continued CR, 12 patients with induced CR, 69.6% of CR rate), and Cyclophosphamide group (5 patients with continued CR, 7 patients with induced CR, 54.5% of CR rate). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. Relapse rate after ASCT was lower in bortezomib group (34.8%) than VAD group (63.1%), cyclophosphamide group (63.6%), and thalidomide group (54.3%). However, there was no significant difference of overall survival among these four groups. Conclusions: Bortezomib-based induction therapy might be more effective for improving CR rate in patients who received single ASCT. A further prospective study should be warranted to confirm whether this augmented response rate with bortezomib-based induction therapy might be translated into survival benefits.

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