Long-Term Outcome of Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Waldenstrom Macroglobulinemia (WM)-a Retrospective Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4661-4661 ◽  
Author(s):  
Charalampia Kyriakou ◽  
Ariane Boumendil ◽  
Herve Finel ◽  
Norbert Schmitz ◽  
Henrik Sengeloev ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Treatment Algorithm ◽  
Disease Status ◽  
Line Treatment ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Reduced Intensity

Abstract WM is an indolent lymphoma that has benefited from the introduction of novel agents with the achievement of higher response rates. However, WM remains incurable with conventional treatment. In addition, patients with high risk disease have either transient short lived responses or are refractory to conventional treatments. Although international treatment recommendations suggest considering allo-SCT in late relapses or in refractory younger patients, the place and timing of allo-SCT in the treatment algorithm of WM remains unclear. The aim of the present study was to analyse the long-term outcome of allo-SCT in WM. Patients and methods: Eligible for this retrospective study were patients aged 18 years or older who had a first reduced intensity (RIC) or myeloablative (MAC) conditioning allo-SCT (10/10 matched donor, sibling or unrelated) for WM between 2001 and 2013 and were registered with the EBMT. Baseline patient, disease and transplant data were collected from MED-A forms. Centers were requested to provide additional diagnostic, treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, prognostic factors for survival were estimated using Cox regression models and for relapse incidence (IR) and non-relapse mortality (NRM) by Fine and Gray models. Results: 260 patients (72% male) fulfilling the inclusion criteria of this study were identified in the database. The median age was 52 (range 19-72) years. Disease status at allo-SCT was sensitive in 78% and refractory in 22% of the patients. Conditioning was reduced-intensity (RIC) in 66%, with PBSC (92%) being the predominant stem cell source (bone marrow 7%, cord blood 1%). Patients receiving RIC were significantly older and had a longer interval between diagnosis and transplant but were otherwise comparable to patients with myeloablative conditioning (MAC). Donors were related in 65% and unrelated in 35% of the transplants. The median number of treatment lines prior to alloSCT was 3. Pretreatment details were available for 118 patients. Of these, first-line treatment was alkylator-based in 80%, purine analogue (PA)-based in 17%, and contained rituximab in 23%; for 2nd-line treatment, these figures were 50%, 36%, and 34%; and for 3rd-line treatment 41%, 32%, and 44%. Less than 10% of the patients had received bortezomib or imide-based regimens in any pretreatment line. At 100 days the cumulative incidence of acute graft versus host disease (aGVHD) grade I-II was 35%, and grade III-IV was 12%. At 2 years the cumulative incidence of chronic GVHD (cGVHD) was 41%. The development of cGVHD did not significantly impact on any outcome on a landmark analysis. After a median follow-up for living patients of 57 months (IQR 31-97), 5-year NRM, IR, progression-free survival (PFS) and overall survival (OS) were 29%, 24%, 47% and 55%. Risk factor analyses considering age, sex, performance status (PS), disease status, pretreatment lines, rituximab exposure, year of transplant, donor, and conditioning identified PS for NRM, disease status for IR, and PS and MAC for OS as significant predictors of an adverse outcome after multivariable adjustment. Although RIC patients tended to have a lower NRM and a better PFS than MAC patients, this was not statistically significant, suggesting that RIC patients had a better survival after relapse. 45 patients were treated with donor lymphocyte infusions (DLI) and results of DLI were reported in 22 patients. Of these, a response was observed in 60%, which was complete in 55%. Conclusions: This large study demonstrates that allo-SCT can effectively induce long-term disease control in heavily pre-treated patients with WM, suggesting that graft-versus-lymphoma effects are active and stable in WM. Accordingly, DLI seems to be a promising treatment option in case of post-transplant disease recurrence. Additional studies are needed to elaborate the place of allo-SCT in the treatment algorithm of WM in the era of novel agents. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long-Term Outcome of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mycosis Fungoides and Sézary Syndrome: The Milan Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4655-4655
Author(s):  
Francesco Onida ◽  
Giorgia Saporiti ◽  
Silvia Alberti Violetti ◽  
Elena Tagliaferri ◽  
Federica Grifoni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Term Outcome ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Reduced Intensity

Abstract Introduction: Although a few novel drugs have recently shown promising activity in mycosis fungoides (MF) and Sézary syndrome (SS), prognosis of patients with advanced stages or refractory disease remain poor, with median survival ranging from 1.4 to 3.4 years (Agar NS et al. JCO 2010). In selected patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative strategy. By decreasing transplant-related mortality, reduced intensity (RIC) and nonmyeloablative conditioning (NMA) regimens lead to better outcomes in comparison to myeloablative ones. Here we report long-term outcome of our RIC allo-HSCT experimental program, initiated in 2001. Patients & Methods: As of July 2018, in our Center 40 patients underwent RIC allo-HSCT from HLA-identical sibling (n=16), unrelated donors (UD, n=22 - fully-matched in 10, 1 or 2-mismatch in 12) or haploidentical related donors (n=2). Median age was 52 years (range 19-66). All patients (24 M and 16 F) had stage IIB/IV refractory MF (n=27) or SS (n=13). Median number of previous treatment lines was 6 (range 2-12) while median time from diagnosis to transplantation was 46 months (range 11-264). The source of stem cells has been peripheral blood in 35 patients (87.5%), bone marrow in 4 (10%) and cord blood in 1 (2.5%). Conditioning regimens included FC/TBI200, pentostatin+TBI200, and fludarabine/melphalan in transplants from HLA-identical sibling donor or UD, whereas the TT/Flu/CTX/TBI200 regimen was used in the haploidentical setting. GvHD prophylaxis included CsA/MMF in all patients, with the addition of ATG in cases with UD and post-transplant CTX (50 mg/kg giorni +3 e +4) in haploidentical setting. Results: Full donor chimerism was obtained in 32 out of 37 evaluable patients, in a median time of 2 months (range 1-12). Acute GvHD occurred in 18 patients out of the 32 evaluable (56%), being of grade III-IV in 9 (28%). Chronic GvHD was observed in 10 patients (31%), being extensive in 4 (12%). Of note, the latter were all patients transplanted from HLA-identical sibling (i.e. without ATG). Following transplantation, a complete remission (CR) was achieved in 26 out of the 37 evaluable patients (70%), of whom 4 experienced relapse at +2 (2 pts), +25 and +35 months, respectively. At the last follow-up, 19 patients were alive and 17 (89%) maintained CR after a median follow-up of 80 months (range 4-210). Out of the 11 patients who did not achieve CR, 9 died from progressive disease (median follow-up of 12 months, range 3-31), 1 from a secondary malignancy, while 1 is still alive with disease 62 months after transplant. Transplant-related death occurred in 7 patients (17%), of whom 5 were in CR. In the whole population, the 5-year OS was 52% (95% CI 34-70) [Fig.1] and the 5-year DFS was 43% (95% CI 27-62). However, when MF and SS were analysed separately, 5-yrs DFS were 30% (95% CI 12-51) and 72% (95% CI 38-99), respectively (Fig.2). Apart from diagnosis, outcome appeared to be primarily associated with chemosensitivity and status of disease at transplantation. Conclusions: After a median follow-up longer than 6.5 years, we confirm the efficacy of RIC allo-HSCT as a powerful therapeutic strategy in inducing and maintaining remission in selected patients with chemosensitive advanced-stage CTCL, with results particularly encouraging in SS. Disclosures Cortelezzi: roche: Consultancy; abbvie: Consultancy; novartis: Consultancy; janssen: Consultancy.

scholarly journals Long-Term Outcome of Allogeneic Stem Cell Transplantation in Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2195-2195
Author(s):  
Sung-Eun Lee ◽  
Sung Soo Park ◽  
Young-Woo Jeon ◽  
Jae-Ho Yoon ◽  
Byung Sik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Pnh Clone

Abstract Background: Although recently, Eculizumab, humanized monoclonal antibody directed against complement component C5, has used increasingly for the patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH), allogeneic stem cell transplantation (allo-SCT) can be curative treatment option especially for PNH patients with combined aplastic anemia (AA). The aim of the present study was to evaluate long-term outcome of allo-SCT in patients with AA/PNH. In addition, patients with classic PNH who underwent allo-SCT in the pre-eculizumab era were also evaluated. Methods: Total of 33 patients with PNH clones underwent allogeneic SCT at our institution between Jan 1998 and Jan 2016. Among them, seven patients had classic PNH and 26 patients with cytopenia had AA/PNH (with bone marrow evidence of a concomitant AA). Results: There were 21 male and 12 female patients with a median age of 34 years (range, 13-56 years). Pre-transplant GPI-AP deficient neutrophils and erythrocytes were 5.6% (0-92) and 21% (0-98.5), respectively. Median white blood cell, absolute neutrophil count, hemoglobin, and platelet at transplant were 2.4×109/L, 0.8×109/L, 7.7 g/dL, and 27×109/L, respectively. Median LDH level was 727 U/L (232-7721 U/L) and 19 (58%) patients had LDH ≥1.5x upper limit of normal. Classic PNH (n=7) and AA/PNH [SAA (n=15), VSAA (n=9), or non-SAA (n=2)] received SCT from HLA-matched sibling (MSD, n=24), unrelated (URD, n=7), or haplo-identical donor (Haplo-SCT, n=2). Since 2003, the conditioning regimen for MSD-SCT was changed from Busulfex (12.8 mg/kg) + cyclophosphamide (CY, 120 mg/kg) to fludarabine (180 mg/m2) + CY (100 mg/kg) + rATG (10 mg/kg). The conditioning regimen for URD-SCT and Haplo-SCT were TBI (800 cGy) + CY (100-120 mg/kg) ± rATG (2.5 mg/kg) and TBI 600cGy + Fludarabine (150 mg/m2) + rATG (5 mg/kg), respectively. After a median follow-up of 57 months (range 6.0-151.3), the 5-year estimated OS rates were 87.9 ± 5.7%. Four patients died of treatment-related mortality (TRM), including acute GVHD (n=1), pneumonia (n = 2), and cerebral hemorrhage (n=1), respectively. Except one patient with early TRM, 32 patients engrafted. Two patients who experienced delayed graft-failure received second transplant and recovered. The cumulative incidence of acute GVHD (≥grade II) and chronic GVHD was 27.3 ± 7.9% and 18.7 ± 7.0%, respectively. Among 25 patients with available follow-up data, PNH clone disappeared at median 3.0 months (range 0.7-45.5) after SCT and reemerging of PNH clones was observed in two patients; one patient showed re-appearance of 2.6% GPI-negative neutrophils at 12 months without PNH symptoms, but disappeared again at 21 months. Another patient suffered from labile graft and received a booster with peripheral blood stem cells. Conclusion: This study showed that long-term transplant outcome in patients with AA/PNH were comparable to that of allogeneic SCT in SAA (the 3-year estimated OS rates were 92.7 and 89 % for MSD-SCT and URD-SCT, respectively) at our institution (ASH Annual Meeting Abstracts 2012;120:4151). Reduced-intensity conditioning regimen was sufficient for the eradication of PNH clone in allogeneic SCT. Therefore, application of allogeneic SCT should be considered in PNH patients with AA in case of availability of well matched donor. Disclosures No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem-Cell Transplantation In AML and MDS Using Myeloablative Versus Reduced Intensity Conditioning: 10 Years Later

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4635-4635
Author(s):  
Avichai Shimoni ◽  
Noga Shem-Tov ◽  
Yulia Volchek ◽  
Ivetta Danylesko ◽  
Ronit Yerushalmi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Reduced Intensity Conditioning ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Long Term Follow Up ◽  
Relapse Rates ◽  
Active Disease ◽  
Reduced Intensity

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. There is paucity of data on the long-term outcome (beyond 10 years) following RIC due to the relative recent introduction of this approach. We have previously reported on the role of dose intensity in a group of 112 patients (pts) with AML/MDS given SCT with different regimens between 1999 and 2004 (ASH 2004, Leukemia 2005). We showed that overall survival (OS) 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 SCT relapse rates. We have now updated SCT outcomes in the same cohort with a median follow up of 10 years (range, 8.5-12.5) in order to better predict long-term outcome and confirm whether late events may have changed the initial conclusions. The median age at SCT was 50 years (18–70). Eighty-five pts had AML and 17 had MDS (IPSS int2 or high). Fifty-eight had active disease at SCT (>10% marrow blasts) and 54 were in remission. The donor was HLA-matched sibling (n=58), 1-Ag mismatched related (n=6) or matched-unrelated (n=48). Twenty-nine pts (26%) had poor risk cytogenetics. Forty-five pts met eligibility criteria for standard MAC and were given intravenous-busulfan (ivBu, 12.8 mg/kg) and cyclophosphamide (BuCy). Sixty-seven pts were considered non-eligible for standard MAC due to advanced age, extensive prior therapy, organ dysfunction or poor performance status. These pts were given RIC with fludarabine and ivBu (6.4 mg/kg, FB2, n=41) or reduced toxicity conditioning (RTC) with fludarabine and myeloablative doses of ivBu (12.8 mg/kg, FB4, n=26). The median age of RIC/RTC and MAC recipients was 55 and 42 years, respectively (p=0.001) and a larger proportion of RIC/RTC recipients had unrelated donors (p=0.01). In all, 38 pts are alive and 74 have died, 48 relapse, 26 non-relapse mortality (NRM). Overall survival (OS) at 10 years was 44% and 31% after MAC and RIC/RTC, respectively (p=0.22). Active disease at SCT and poor-risk cytogenetics were the most significant factors predicting reduced OS in multivariable analysis, HR 2.0 (p=0.05) and 2.7 (p=0.003), respectively. Advanced age, secondary disease, donor and conditioning type had no prognostic significance. MAC and RIC/RTC had similar outcomes when leukemia was in remission at SCT; 10-year OS been 47%, 50% and 47% after BuCy, FB4, and FB2, respectively (p=0.97). OS rates of pts with active disease at SCT was 43%, 19% and 0%, respectively (p=0.01) suggesting an advantage for more intense regimens in this setting. Relapse rates were higher after RIC/RTC than MAC throughout the follow-up period. The rate was 30% and 18%, 1 year after SCT (p=0.03), 37% and 20% after 2 years (p=0.08), 49% and 27% after 5 years (p=0.02) and 51% and 29% after 10 years (p=0.02), respectively. NRM rates were higher after MAC than RIC/RTC in the initial 2 years after SCT but approached each other in the late post SCT course. NRM rate was 22% and 9%, 1 year after SCT (p=0.05), 22 and 10% after 2 years (p=0.08), 22% and 15% after 5 years (p=0.27), and 27% and 19% after 10 years (p=0.35), respectively. Thus, OS was similar within the first 2 years after SCT, 56% and 52% after MAC and RIC/RTC, respectively (p=0.86), but there was a trend for better OS after MAC later on, 51% and 36%, 5 years after SCT (p=0.26) and 44% and 31%, 10 years after SCT (p=0.22), respectively. Forty-seven pts were alive 5 years after SCT (42%). Nine of them died later on. Four of 24 RIC/RTC survivors at this point later died, 3 of second malignancies, 1 of relapse. Five of 23 MAC survivors at 5 years later died, 2 of relapse, 2 of chronic GVHD, 1 of MI. For pts surviving 5 years after SCT, the expected OS for the next 5 years was 86% and 87%, respectively (p=0.76). In conclusion, with a long-term follow-up of more than 10 years, RIC/RTC is an acceptable alternative to MAC in ineligible pts. NRM is lower after RIC/RTC in the early post SCT period, but late NRM negates this early advantage. Relapse rates are higher after RIC/RTC throughout the course. Due to these observations, it seems an advantage of MAC may become apparent 5-10 years after SCT. Pts who are alive 5 years after SCT can expect similarly good further OS with both approaches. Long-term follow-up studies (beyond 10 years) are of significant importance when assessing SCT outcomes in general and RTC SCT in particular. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation For Cytogenetically Normal Acute Myeloid Leukemia: Impact Of FLT3 and NPM1 Mutational Status

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2104-2104 ◽  
Author(s):  
Philipp Hemmati ◽  
Theis H. Terwey ◽  
Lam G. Vuong ◽  
Philipp D le Coutre ◽  
Bernd Dörken ◽  
...  
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Wild Type ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Remission Status ◽  
Mutational Status

Abstract Purpose Cytogenetic abnormalities as detected by conventional karyotyping are among the strongest predictors for the long-term outcome of patients (pts) with acute myeloid leukemia (AML). However, up to 50% of pts are cytogenetically normal (CN) and the screening for mutations of the FLT3 and the NPM1 genes allowed to further dissect this heterogeneous group. Allogeneic stem cell transplantation (alloSCT) has become an integral part of the post-remission therapy for pts with intermediate or high-risk AML in case an HLA-compatible donor is available. Here, we analyzed the impact FLT3 and NPM1 mutations on the outcome of pts with CN-AML who underwent alloSCT at our center between 2006 and 2013. Pts and Methods Follow-up data of all pts were prospectively collected in a computer database and retrospectively analyzed as of June 30th, 2013. 101 pts (46 female, 55 male) with a median age of 54 (range: 18-75) years with CN-AML were included. 71 pts had de novo AML, whereas 30 pts had secondary or therapy-related AML. All pts were treated in a German multicenter AML trial and received at least two courses of induction therapy. The FLT3 and NPM1 mutational status was as follows: 14 pts were FLT3-mutated/NPM1 wild-type, 15 pts were NPM1 mutated/FLT3 wild-type, 22 pts were FLT3-mutated/NPM1 mutated, and 50 pts were wild-type for both FLT3 and NPM1. At alloSCT, 62 pts were in first complete remission (CR1), 16 pts were in CR2, and 23 pts had refractory disease. In 96 pts alloSCT was performed using peripheral blood stem cells (PBSCs), 5 pts received a bone marrow (BM) graft. Conditioning consisted of standard myeloablative conditioning (MAC) (6x2 Gy TBI and 2x60 mg/m2 cyclophosphamide) in 24 pts. 77 pts received reduced intensity conditioning (RIC) (2x4 mg/kg oral busulfan, 6x30 mg/m2 fludarabine and 4x10 mg/kg ATG). A matched related donor was available for 27 pts, whereas 55 pts or 19 pts were transplanted from a matched-unrelated or mismatched unrelated donor. Results After a median follow-up of 11 (range: 1-83) months for the surviving pts, 64 pts are alive and in CR. Causes of death were relapse or NRM in 26 pts or 12 pts, respectively. At 1, 3 and 5 years projected overall survival (OS) or disease-free survival (DFS) of the entire cohort was 67% (57-77%), 58% (46-69%), and 54% (42-67%) or 60% (51-71%), 57% (47-68%), or 50% (37-54%). At the same time points the cumulative incidence of relapse (CIR) or non-relapse mortality (CINRM) was 27% (19-38%), 30% (22-43%), and 37% (36-52%) or 12% (6-21%) remaining stable thereafter. Subgroup analysis showed that the presence of a NPM1 mutation in the absence of mutated FLT3 is associated with a significantly lower CIR, i.e. 8%, at 3 years. In the other subgroups the CIR ranges between 32% for pts lacking FLT3 and NPM1 mutations and 37% for pts carrying both mutations (p=0.002). In univariate analysis, pts with refractory disease had a significantly lower DFS (p=0.0002) and a higher relapse incidence (p=0.0001) as compared to pts transplanted in CR. All other factors examined, i.e. AML subtype, stem cell source, type of conditioning, donor/HLA-match were not associated with OS, DFS, or relapse incidence. Notably, there was no correlation between FLT3 or NPM1 mutational status and remission status at the time of alloSCT. OS did not differ significantly between the four subgroups due to an increased NRM in patients with NPM1-mutated CN-AML. Finally, in multivariate analysis only remission status was identified as an independent prognosticator for DFS and relapse incidence, whereas alloSCT from a mismatched unrelated donor predicted a higher NRM. Conclusions Taken together, our results indicate that pts with high-risk AML, as defined by the presence of a FLT3-mutation, may achieve durable long-term remissions following either MAC and RIC-alloSCT from related an unrelated donors. In turn, the presence of a mutation of the FLT3 gene may not per se predict a poor outcome in this setting. In contrast, remission status is among the strongest predictors for long-term outcome in patients with CN-AML undergoing alloSCT. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem-Cell Transplantation in AML and MDS Using Myeloablative Versus Reduced Intensity Conditioning: Long-Term Follow-up.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2166-2166
Author(s):  
Avichai Shimoni ◽  
Avital Rand ◽  
Izhar Hardan ◽  
Noga Shem-Tov ◽  
Yulia Volchek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloablative Conditioning ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Relapse Rates ◽  
Active Disease

Abstract Allogeneic stem-cell transplantation (SCT) with both myeloablative and reducedintensity conditioning (RIC) is effective therapy in AML and MDS. However, the relative merits of each may differ in different settings and the long-term outcome is less defined. 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 regimens (Leukemia 2006). We showed that survival was similar with myeloablative conditioning 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. We have now updated SCT outcomes with an additional 3-year follow-up in the same cohort, to better predict long-term outcome and confirm that late events did not change the initial conclusions. The study group included 112 consecutive pts with AML/ MDS transplanted over a 5-year period. The median age at SCT was 50 years (18–70). Eighty-five pts had AML (39 secondary) and 17 had MDS (all with excess of blasts). Fiftyeight had active disease at SCT (>10% marrow blasts) and 54 were in remission. The donor was HLA-matched sibling (n=58), 1-ag mismatched related (n=6) and matched-unrelated (n=48). Forty-five pts met eligibility criteria for standard myeloablative conditioning and were given intravenous-busulfan (12.8 mg/kg) and cyclophosphamide (ivBuCy). Sixtyseven pts were considered non-eligible for standard myeloablation due to advanced age (over 55 years for sibling SCT or over 50 years for mismatched or unrelated SCT), extensive prior therapy, organ dysfunction, recent fungal infection or poor performance status. These pts were given RIC with fludarabine and intravenous-busulfan (6.4 mg/kg, FB2, n=41) or modified myeloablative regimen with fludarabine and myeloablative doses of intravenous-busulfan (12.8 mg/kg, FB4, n=26). The median age of this group was 55 years compared with 42 years in the first group, and a larger proportion had SCT from unrelated donors. With a median follow-up of 5.1 years (3.3–8.6), 45 pts are alive and 67 have died (45 relapse, 22 non-relapse causes). Overall survival (OS) at 5 years was 48%, 31%, and 38% after ivBuCy, FB4, and FB2, respectively (p=NS). Active disease at SCT and poor-risk cytogenetics were the most significant factors predicting reduced survival in multivariable analysis with hazard ratios of 3.5 (p=0.0001) and 1.7 (p=0.04), respectively. Advanced age, secondary disease, donor and conditioning type had no prognostic significance. Myeloablative conditioning and RIC had similar outcomes when leukemia was in remission at SCT; estimated 5-year OS been 49%, 50% and 58% after ivBuCy, FB4, and FB2, respectively (p=NS). There was a non-statistically significant trend for lower non-relapse mortality (NRM) but higher relapse rate with FB2 resulting in similar OS in this setting. However pts with active disease could only be salvaged by myeloablative regimens (classical or modified). Among the later group, OS was 41% and 19% after ivBuCy and FB4, respectively, but no FB2 recipient survived (p=0.009). This was related to significantly higher relapse rates with the less intensive regimens in this setting (p=0.0005), while NRM was similar. These observations confirm with a longterm follow-up that RIC is associated with favorable outcome and low toxicity in pts in remission at SCT and therefore can be further studied in prospective trials comparing it to myeloablative regimens even in pts eligible for the later. However, RIC is a poor option for pts with active disease. Pts with active disease not eligible for standard myeloablation can still tolerate the modified myeloablative regimen (FB4) and a fraction can be salvaged. These observations merit further study in randomized prospective studies.

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