Background: We started a randomized phase II trial NCT01572662 that compared the safety of two myeloablative fractionated (“timed-sequential”) busulfan with fludarabine (Bu-Flu) conditioning ...regimens: one with a lower dose of busulfan (area under the curve AUC of 16 000 μmol.min; 16K arm) and one with a higher dose (AUC of 20 000 μmol.min; 20K arm). After 49 patients were treated on the 16K group and 48 patients on the 20K group, the randomization was stopped as the higher dose arm was found to be as safe as the lower dose arm. The outcomes of those patients were previously reported, with the primary endpoint of interest being day 100 non-relapse mortality (NRM). The trial then continued enrolment as a single-arm study with increased accrual onto the higher dose arm. The current paper reports long-term outcomes of a total of 150 patients treated on the higher dose arm with an extended median follow-up of over 3.5 years.
Methods: Patients with hematological malignancies up to 75 years of age were included. Bu dosing was determined on the basis of pharmacokinetic (PK) analyses conducted after day -13 and day -6 dose to achieve target AUC 20 000 ± 12% μmol.min (20K arm). On days −13 and −12, patients received 80 mg/m2 Bu IV daily as outpatient. Then, Flu 40 mg/m2 and Bu IV once daily were given as inpatient from day −6 though −3. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus from day −2 and methotrexate on days 1, 3, 6, and 11.
Results: The median age was 61 years (interquartile range, 55-67); most were males (91; 61%) had an unrelated donor (n=93, 62%) and received peripheral blood graft (n=110, 73.3%). The most common diagnoses were acute myeloid leukemia (AML) and myelodysplastic syndrome (n = 88, 58.7%). Among AML, 41% (n=24) were in CR, 44% (n=26) had primary induction failure and 15% (n=9) had relapsed disease without attaining CR before HCT. Over half had HCT-Specific Comorbidity Index (HCT-CI) >3 (n=79, 52.7%).
Estimated relapse, NRM, and overall survival (OS) were 40% (95% confidence interval (CI), 32.1%-47.9%), 22% (95% CI, 15.3%-28.7%), and 49.1% (95% CI, 41.7%-57.8%) at 3 years Table. The highest relapse rate at 3 years was noted in patients with myeloma (70.6%), followed by MDS (51.7%), and lymphoma (46.2%), while it was the lowest in myelofibrosis (13.6%). Among AML patients not in CR, the rate of relapse was not higher than those who were in CR (37.1% and 41.7%, respectively at 3 years). NRM at 3 years ranged from 7.7% (lymphoma) to 37.1% (AML, not in CR). Lymphoma patients had the lowest NRM (7.7%) and the best OS (69.2%) at 3 years, while AML patients not in CR had the highest NRM (37.1%) and the lowest OS (31.4%) Figure. Patients with HCT-CI 0-2 had lower NRM (14.1%; 95% CI, 5.9%-22.3%) and better OS (57.2%; 95% CI, 46.7%-70.1%) than those with HCT-CI > 3 (NRM: 29.1%; 95% CI, 19%-39.2% & OS: 41.7%; 95% CI, 32.2%-54.2%).
Day 100 cumulative incidence of grade II-V acute GVHD was 38% (95% CI, 30.2%-45.8%), grade III-IV was 11.3% (95% CI, 6.2%- 16.4%). At 3 years, cumulative incidence of extensive chronic GVHD was 27% (95% CI, 20%-34%), bronchiolitis obliterans was 4.7% (95% CI, 1.3%-8.1%), and secondary malignancies was 8.7% (95% CI, 4.1%-13.2%).
Conclusion: The fractionated myeloablative Bu-Flu conditioning regimen is well tolerated and leads to acceptable risk of NRM, relapse and long term survival in older patients, those with high risk disease and high comorbidities. Acknowledging the high risk study population, the long term outcomes, although acceptable, provide a framework to further improve upon. Modifications of this fractionated Bu-Flu regimen to further enhance its efficacy (with the addition of other chemotherapy agents) while reducing the toxicity and risk of NRM (with an inclusion of novel GVHD prophylaxis regimens) are currently being investigated.
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Mehta:Incyte: Research Funding; Kadmon: Research Funding; CSL Behring: Research Funding. Alousi:Therakos: Research Funding; Alexion: Honoraria; Incyte: Honoraria, Research Funding. Bashir:Celgene: Research Funding; Amgen: Other: Advisory Board; KITE: Other: Advisory Board; Purdue: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Acrotech: Research Funding; StemLine: Research Funding. Hosing:NKARTA Inc.: Consultancy. Kebriaei:Novartis: Other: Served on advisory board; Amgen: Other: Research Support; Jazz: Consultancy; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board. Oran:Celgene: Consultancy; Arog Pharmaceuticals: Research Funding; ASTEX: Research Funding. Qazilbash:Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy; Bioline: Research Funding; Janssen: Research Funding. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Adaptimmune: Membership on an entity’s Board of Directors or advisory committees; Zelluna: Membership on an entity’s Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; Johnson and Johnson: Consultancy; Actinium: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; Genzyme: Speakers Bureau; DKMS America: Membership on an entity’s Board of Directors or advisory committees. Popat:Bayer: Research Funding; Novartis: Research Funding.
The use of mismatched donors is rapidly increasing for pts with hematological malignancies in need of allo HCT. Here we compared the outcomes of melphalan based reduced-intensity conditioning (RIC) ...using haplo-identical transplantation with post transplant cyclophosphamide (PTCy) and haplo cord transplantation where a CBU graft is supplemented with CD34 selected haplo-identical cells to accelerate engraftment.
Patients and Methods:
217 pts underwent Haplo transplants at MDACC. Conditioning consisted of fludarabine (flu)-melphalan 140 mg/m2 (mel) (47) flu-mel-thiotepa (129), or flu-mel-TBI 200 cGy (37). Dose of Mel was 140 mg/m2 for 128 and 100 mg/m2 for 88.GVHD prophylaxis was PTCy, tacro and mycophenolate (MMF). Graft source was bone marrow in 206 pts and PBSC in 11. 224 pts underwent HC HCT at Weill Cornell, New York and at the University of Chicago. Conditioning consisted of Flu-Mel (178) or Flu-Mel-TBI 400 cGy (46). Dose of Mel was 140 mg/m2. GVHD prophylaxis was ATG, tacro and MMF. Pt characteristics are in Table 1. 58% of haplo vs 67% of HC recipients had AML or MDS (P=0.01). 36% of HC vs 20% of Haplo were 60 and older (P=0.007) and 56% of HC vs 34% of Haplo had HCTCI >=3 (P=0.0000). Median F/U was 30 mo for HC vs 21 mo for Haplo group.
Results
Median time to neutrophil recovery was 11 days after HC vs 19 after Haplo SCT (p<0.001). Time to plt recovery was 22 d after HC vs 26 Haplo SCT (p =0.001). CI of gr II-IV aGVHD was 21% by d150 after HC vs35% after Haplo SCT (p=0.0005). CI of gr III-IV aGVHD was identical at 11% in each group. CI of all chronic GVHD was 2% at one year after HC vs 16% after Haplo SCT (p<0.001). Overall survival, PFS, CI Relapse and NRM were not significantly different. In multivariable analysis, graft source did not correlate with OS, PFS, Relapse or NRM. In multivariable analysis Disease Risk Index (DRI) and Age>=60 were the major determinants of OS and PFS. For patients with Low and Intermediate DRI under age 60, 2 Y OS was 60% for haplo and 59% for HC.
Conclusions: Melphalan based RIC result in similar and encouraging survival and progression free survival with HC or haplo grafts. HC HCT was associated with more rapid neutrophil and a lower rate of acute and of chronic GVHD.
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Liu:Karyopharm: Research Funding; BMS: Research Funding.
The CXCR4 inhibitor plerixafor in combination with G-CSF disrupts stroma-leukemia interactions, mobilizing leukemia cells from their niche microenvironment. This combination in conjunction with ...chemotherapy has been investigated in clinical trials in AML. We recently reported a phase 1/2 study of CXCR4 inhibition combined with chemotherapy prior to allogeneic stem cell transplantation (allo-SCT) (G-CSF-plerixafor (G+P) plus busulfan-fludarabine (Bu+Flu), Konopleva, et al. BMT 2015) and confirmed that patients who had not achieved remission at the time of transplant (“non-CR”) had poorer outcome than patients who were in remission at the time of allo-SCT (“CR”). Similar results have been reported in other clinical studies. Risk factors, such as the presence of circulating blasts and unfavorable cytogenetics are associated with poor outcome, but the molecular responses in patients treated with CXCR4 inhibitor and conditioning chemotherapy prior to allo-SCT are unknown. We investigated the hypothesis that the CXCR4 inhibition-driven preparative regimen modulates distinct signaling networks, which vary depending on disease status.
Utilizing reverse phase protein array (RPPA), we profiled 157 proteins in 36 cellular signaling and functional groups in samples collected from ten AML patients who were studied in the phase 1/2 trial (Table1). Five CR patients had less than 1% blasts in bone marrow (BM) and no blasts in peripheral blood (PB) before conditioning regimen (baseline, day -9). Five non-CR patients had BM blasts ranging from 10-72% and PB blasts from 0-45%. Here we denote samples from “CR” patients as “normal” and from “non-CR” patient as “AML”. All “AML” patients with blasts had persistent blasts after G+P plus conditioning, ranging from 4-64%. However, four of five “AML” and five “normal” patients achieved complete response to allo-SCT. Engraftment was observed in all patients. Disease progression following allo-SCT was observed in four of five “AML” but not in “normal” patients. Overall survival in “AML” was significantly shorter than in “normal” patients (non-CR = 260 ± 55 days, CR = 2028 ± 103 days, P < 0.001).
RPPA analysis of samples prior to conditioning (day -9) revealed that 9 proteins in 9 signaling pathways were expressed differently in “normal” and “AML” samples. Among them, c-KIT, 53BP1, a P53-binding DNA repair protein, and CIAP (a SMAC and IAP family member) had significantly higher expression in “AML”.
G+P treatment significantly modulated 7 proteins in 4 pathways in “AML” samples, and 22 proteins in 13 signaling and functional groups in “normal” samples (Fig 1A). As a result, 22 proteins in 14 signaling and functional groups were differentially expressed in “AML” and “normal” samples post G+P treatment (day -7) (Fig 1B). Among the top 10 distinct proteins, PI3Kp110A, P53BP1, SMAD1 and p-C-JUN S73 had higher expression, and P38MAPK, p-HER2 Y1248, P-CADHERIN, SYK, P21 and TAU had lower expression in “AML” samples.
Treatment with G+P plus Bu+Flu conditioning modulated 10 proteins in 7 signaling pathways in “AML” samples, and altered 40 proteins in 13 signaling pathways in “normal” samples (Fig 1C). As a result, G+P plus Bu+Flu conditioning caused significant differences in expression of 16 proteins in 14 signaling and functional groups in “AML” vs. “normal” samples (day -3) (Fig 1D). Among the top 10 distinct proteins, PI3Kp110A, XRCC1, p-ERA S118, 53BP1, and BCL2 had higher expression, and MIG6, SYK, TAU, p-AKT T308 and MEK1 had lower expression in “AML” samples. Notably, c-KIT and 53BP1 in “AML” baseline samples were persistently expressed at high levels in samples from G+P and G+P plus Bu+Flu treated patients, suggesting that c-KIT and 53BP1 mediated signaling might play a role in therapeutic resistance and disease relapse in patients with active disease at the time of transplant.
In summary, CXCR4 inhibition combined with Bu+Flu conditioning triggered distinct molecular responses, resulting in differential signaling between “normal” and “AML” cells prior to allo-SCT. The persistence of c-KIT and 53BP1 might play a role in resistance and contribute to relapse in AML.
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No relevant conflicts of interest to declare.
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Background: Scoring systems, such as DIPSS-plus, prognosticate outcomes of myelofibrosis (MF) at diagnosis and at transplant. In this study, we evaluated the impact of individual ...components of these scoring systems, along with other factors previously reported to significantly prognosticate transplant outcomes in patients with MF. Methods: We identified 65 consecutive patients conditioned uniformly with Fludarabine(40 mg/m2X4days)/Busulfan(AUC-4000X4days) and ATG(MUD), tacroliumus and methotrexate for GVHD prophylaxis for allo-SCT during 2007-2019 at MD Anderson Cancer Center, USA. Associations between factors of interest and overall survival(OS), cumulative-incidence-of-relapse(relapse) and non-relapse mortality(NRM) were evaluated. Results: At transpant, median age was 61(range = 27-73) years; 42% were transfusion-dependent, 31% had secondary MF and 53% patients were intermediate2 and 42% were high-risk by DIPSS-plus. Forty percent of the 35 patients who had 28-gene panel tested had atleast one high-molecular-risk mutation, per MIPSS. Median follow-up for survivors was 35.6 months(range = 0.5-123). One-year and 5-year rates for OS were 78% and 51%, for relapse were 21% and 30%, and for NRM were 16% and 28%, respectively. Our multivariate analysis shows the following significant prognostic factors: HCT-CI > 3hazard ratio(95% CI):5.63(1.48-21.27)p = 0.011, peripheral-blood blasts≥5%5.98(1.33-26.89)p = 0.020 and prior splenectomy6.41(1.83-22.47)p = 0.004 were associated with worse OS. Matched-unrelated donor4.07 (1.38-12.08)p = 0.011) and mismatched-unrelated donor7.36 (1.36-39.83)p = 0.021 versus matched-related donor as well as peripheral blasts≥5%4.10(1.00-16.83)p = 0.05 were associated with worse NRM. Diagnosis to transplant duration > 12months5.81(1.33-25.420)p = 0.020 was associated with higher relapse. Presence of 2 or more poor-risk mutations 6.39(1.35-30.21)p = 0.019 predicted higher relapse on univariate analysis and was not included in multivariate analysis(as data was available in 35 patients only). Conclusions: Of the IPSS-components used at diagnosis, only peripheral-blood blasts(at threshold ≥5%) was associated with worse outcome(OS and NRM). Unrelated-donor source was associated with higher NRM. Diagnosis to transplant duration > 12months predicted higher relapse. The effect of mutations needs to be validated in a bigger study.
In patients with AML with FMS‐like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes ...after transplant remains unclear. We identified 200 patients with FLT3‐AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n = 119), high‐risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR‐HR, n = 31), and morphological evidence of active disease (AD, n = 50). The median follow‐up was 27 months, and the 2‐year overall and progression‐free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR‐HR FLT3 MRD positive group (72%), followed by CR‐HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre‐transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3‐AML.
Abstract 362
Delayed engraftment and low rates of platelet transfusion independence are frequently observed after CB transplantation (CBT). We conducted a study of ex-vivo co-culture of CB ...mononuclear cells with either third party haploidentical family member marrow derived MSCs (N=8) or off-the-shelf mesenchymal progenitor cells (MPCs) from Angioblast (N=24). Patients received a double cord blood transplant, with one of the 2 units undergoing ex vivo expansion using this system. MSCs create a microenvironment that promotes expansion and fosters the differentiation of hematopoietic cells. Patients must have had two CB units matched in at least 4/6 HLA antigens, with a minimum of 1×107 TNC/Kg per unit.
Diagnoses were AML/MDS (n=21), ALL (n=6), NHL (n=2), CLL (n=2), and HD (n=1). Fourteen patients (44%) were in CR (CR1, n=3, CR2 or more, n=11) and 18 (56%) had active disease at CBT. Preparative regimen: myeloablative fludarabine, melphalan, thiotepa and ATG (n=32), with rituximab in the 4 NHL/CLL cases. GVHD prophylaxis: tacrolimus and MMF. Median weight was 75.2 Kg (range, 15–118) and median age was 35.3 years (2.8-62 years). Donor-recipient HLA matching was 6 of 6 in 5%, 5 of 6 in 28% and 4 of 6 in 67% of the cases, respectively.
Ex-vivo EXP: 100 ml of marrow was aspirated from the family donor and MSCs generated in ten T175 flasks, which took ∼21 days (n=8) or one vial of Angioblast MPCs was thawed and expanded to confluence in 10 flasks within 4 days (n=24). The CB unit with the lowest TNC dose was then thawed, divided into 10 fractions, and each placed into 1 flask containing the confluent layers of MSCs in expansion media with SCF, FLT3-ligand, G-CSF and TPO. After 7 days at 37°C, the non-adherent cells were removed from each flask, placed into each of ten one-liter Teflon-coated culture bags (American Fluoroseal) and cultured for an additional 7 days (14 days total), while 50 ml of media/growth factors was added to the flasks to culture the remaining adherent layer during that time period. On day 14 the cells from the bags and the flasks were combined, washed and infused along with a second unmanipulated CB unit.
The median number of total nucleated cell (TNC) and CD34+ cells infused/Kg in unmanipulated CB was 2.35 × 107 (range 0.2–8.2) and 0.95 × 105 (range 0–4). The median number of TNC and CD34+ cells infused/Kg after EXP was 5.8 × 107 (range, 0.3–14.4) and 8.7 × 105 (range, 0–93.4). This represented a median expansion of 14-fold (range 1–30) for TNC and 40-fold (range 4–140) for the CD34+ cells. Median time to neutrophil and platelet engraftment was 15 days (range 9–42) and 40 days (range 13–62). There were no toxicities attributable to the EXP cells. Thirty-one (97%) and 26 (81%) of all patients engrafted neutrophils and platelets, respectively. One patient died before engraftment. Thirty and one-hundred day non-relapse mortality is respectively 6% and 19%. Median donor(s) chimerism was 100% in the mononuclear, T lymphocyte and myeloid cell populations. On transplant day+21, EXP unit contributed with a mean of 19% of mononuclear cell, 16% of T cell, and 14% of myeloid chimerism. Subsequently, hematopoiesis was increasingly derived from the unexpanded unit with long-term engraftment provided by the unexpanded unit by six months posttransplant.
Acute grade II-IV and III-IV GVHD rate was 50% and 16%; 25% of the grade II-IV GVHDs occurred beyond 100 days, and two patients developed chronic GVHD. With a median follow-up of 9 months, 11 patients are alive; actuarial one-year survival is 40%. Mortality was due to relapse in 26% and non-relapse causes in 74% of patients.
MSC-CB Exp is feasible and leads to fast engraftment of neutrophils and platelets, and high-rates of platelet transfusion independence.
No relevant conflicts of interest to declare.
Conditioning regimens contribute significantly to outcomes following allogeneic stem cell transplantation (allo-SCT). Reduced-intensity conditioning (RIC) regimens provide lower toxicity at the cost ...of reduced efficacy compared with myeloablative conditioning (MAC) regimens. However, because pre-transplant prognostic variables often determine the conditioning regimen, studies of RIC vs. MAC have been inconclusive. We present a retrospective analysis of 242 acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients, 112 of whom were in 56 pairs matched using propensity scores, to account for variation that may confound clinical outcomes. The uniform conditioning regimens consisted of fludarabine with pharmacokinetic (PK)-guided intravenous busulfan (Bu). The RIC and MAC regimens were dosed at the average daily area under the concentration-vs-time curve (AUC) of 4000 µMol min and 5000-6000 µMol min, or total course AUC of 16,000 µMol min and 20,000-24,000 µMol min, respectively; PK-guided dosing removes overlap in systemic Bu exposure. When patients' data were propensity-matched, there was a trend toward significantly increased full donor chimerism and decreased chronic graft vs. host disease in RIC, and no significant differences in progression free survival and overall survival between RIC and MAC. Our results also elucidate the efficacy of PK-guided-dosing in the setting of allo-SCT for AML and MDS.
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Background: Traditionally, pre-transplant conditioning regimen is given over 4-6 days before hematopoietic cell transplant (HCT). Delivering higher dose chemotherapy preparative regimen over a ...longer time period has not been tested previously. We hypothesized that the delivery of myeloablative dose of busulfan over a 3-week period may reduce toxicity and non-relapse mortality (NRM), without affecting relapse, and tested this in a prospective phase II study.
Methods: Patients between 18 and 70 years of age with hematological malignancies and adequate organ function, with 8/8-HLA matched related or unrelated donor were eligible. They received a fixed dose of busulfan 80mg/m2 as outpatient on days -20 and -13. Then, fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. GVHD prophylaxis was cyclophosphamide (PTCy) 50mg/kg on days 3 and 4 and tacrolimus. Mycophenolate mofetil (MMF) was added to later unrelated donor recipients. All patients received standard supportive care. The primary endpoint was day 100 NRM.
Results: We enrolled 52 patients with a median age of 62 (range, 39-69) years. Almost half (n=25, 48%) had AML or MDS and the other half (n=26, 50%) had had CML or MPD; 1 (2%) had multiple myeloma. Low, intermediate, high and very-high disease risk index (DRI) was present in 3 (6%), 34 (65%), 14 (27%) and 1 (2%). HCT-comorbidity index was >3 in 23 (44%) and 1-2 (n=23, 44%). A majority (n=32, 62%) had an unrelated donor.
With a median follow up of 14 months (range, 3-23), NRM at day 100 was 1.9% (n=1) and 8% (95% CI, 0-15) at 1 year. Overall survival, progression-free survival and relapse at 1-year were 83% (95% CI, 73-95%), 78% (95% CI, 67-91%), and 14% (95% CI, 4-24%), respectively Table.
There were no graft failures. The median time to neutrophil engraftment was 17 days (range, 13-33) and that of platelets (> 20K/µL, n=45) was 24 days (range, 9-266). Day 100 grade II-IV and III-IV acute GVHD rates were 37% (95% CI, 23-50%) and 6% (95% CI, 0-12%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 9% (95% CI, 0-17%) and 7% (95% CI, 0-14%), respectively. Overall survival at 1-year differed significantly among patients with low/intermediate DRI (94%; 87-100%) and those with high/very high DRI (53%; 31-91%), P=0.001.
Conclusion: Myeloablative fractionated busulfan regimen with PTCy GVHD prophylaxis is feasible in older patients, has low incidence of severe acute GVHD, chronic GVHD, and NRM and results in promising overall survival.
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Popat:Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; StemLine: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Ciurea:Miltenyi: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder. Kebriaei:Amgen: Research Funding; Pfizer: Honoraria; Jazz: Consultancy; Kite: Honoraria. Nieto:Astra-Zeneca: Research Funding; Affimed: Research Funding; Affimed: Consultancy; Novartis: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Astex pharmaceuticals: Research Funding. Qazilbash:Autolous: Consultancy; Bioclinica: Consultancy; Speaker: Other: Speaker; Amgen: Other: Advisory Board. Molldrem:M. D. Anderson & Astellas Pharma: Other: Royalties.
Fludarabine & Busulfan as conditioning agent prior to transplant
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