scholarly journals Primary Plerixafor Mobilization In Autologous Hematopoietic Cell Transplant Candidates At High Risk For Mobilization Failure

2010 ◽  
Vol 16 (2) ◽  
pp. S207
Author(s):  
J. Shapiro ◽  
R. Bookout ◽  
J. Perkins ◽  
E. Ayala ◽  
M. Alsina ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Transplant Candidates

scholarly journals Risk Factors for Transplant-Associated Thrombotic Microangiopathy after Autologous Hematopoietic Cell Transplant in High-Risk Neuroblastoma

2019 ◽  
Vol 25 (10) ◽  
pp. 2031-2039 ◽  
Author(s):  
Vanessa P. Tolbert ◽  
Christopher C. Dvorak ◽  
Carla Golden ◽  
Madhav Vissa ◽  
Nura El-Haj ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Thrombotic Microangiopathy ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

scholarly journals Pre-Salvage ISS and Other Important Outcome Predictors in CD34 Selected Allogeneic Hematopoietic Cell Transplant for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3473-3473
Author(s):  
Adam Bryant ◽  
Patrick Hilden ◽  
Sergio Giralt ◽  
Miguel-Angel Perales ◽  
Guenther Koehne
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Older Age ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Term Survival ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
The Impact

Abstract Introduction Despite recent therapeutic advances Multiple Myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to imid or proteasome inhibitor therapies are universally dismal.1 Allogeneic hematopoietic cell transplant (alloHCT) remains the only curative MM treatment but has been associated with historically high rates of GVHD and of non-relapse mortality (NRM), exceeding 40% in some series.2 Although these rates have decreased in recent years, the potential morbidity and mortality associated with alloHCT and the increasing availability of alternative non-transplant therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on clinical outcomes in a large cohort of relapsed/refractory (RR) MM patients who underwent CD34+ selected alloHCT at our institution. Methods This retrospective study included all MM patients who had CD34+ selected alloHCT from Jun 2010 to Dec 2015. Patients were conditioned with targeted dose busulfan (0.8 mg/kg x 10), melphalan (70 mg/m2 x 2) and fludarabine (25mg/m2 x 5) followed by infusion of a CD34+ selected peripheral blood stem cell graft, without post alloHCT GVHD prophylaxis. Estimates were given using the Kaplan-Meier and cumulative incidence methods. Competing risks for relapse, NRM, and GVHD were death, relapse, and relapse or death respectively. The log-rank and Gray's test were used to assess univariable associations. GVHD by 6 months was assessed via a landmark analysis. Results Our 73 patient cohort had a median age of 55 (37-66) and was mostly male (74%). Most patients had low risk MM by ISS (50/66, 76%) and intermediate risk MM by R-ISS (45/66, 68%) at pre-salvage assessment. Patients had a median of 4 (2-9) pre-alloHCT lines of therapy and were evenly split between patients in PR and in VGPR or CR at time of alloHCT (50% and 49%). Median HCT-CI score was 2 (range 0-6) with the majority of patients graded as intermediate or high risk (score ≥1; 55/73, 75%). At a median follow-up in survivors of 35 months (12-84) OS and PFS rates were 70% and 53% at 1 year (95% CI 58-79, 41-64) and 50% and 30% at 3 years, respectively (38-62, 19-41). The cumulative incidences of relapse were 25% and 47% at 1 and 3 years, respectively (16-35, 35-58), and 1 year NRM was 22% (13-32). Deaths were balanced between relapse and non-relapse causes (54% and 46% respectively). Incidence of grade II-IV acute GVHD was 7% at 100 days (3-14), and of chronic GVHD was 8% at 1 year (3-16). In univariable analysis, intermediate-high risk ISS assessed prior pre-alloHCT salvage therapy was associated with lower OS (3 year 30 v 54%, p=0.037), lower PFS (3 year 9 v 33%, p=0.013), and greater relapse incidence (3 year 72 v 39%, p=0.004). Older age and GVHD prior to 6 months were also associated with lower OS; older age, more heavily pre-treated disease, and worse disease status at alloHCT were associated with lower PFS; and heavier pre-alloHCT treatment was also associated with higher relapse (Table 1). Higher HCTCI was not associated with increased NRM (1 year 22 v 16 v 27% for HCTCT 0, 1-2, ≥3 respectively; p = 0.863). Discussion We describe a cohort of high-risk heavily pretreated RRMM patients with durable OS (50% at 3 years), comparatively low PFS (30% at 3 years), and historically improved rates of NRM (22% at 1 year). We also importantly identified numerous pre-alloHCT variables that were associated with survival, PFS, and relapse. Amongst these, poor ISS measured prior to pre-alloHCT salvage was consistently associated with worse survival and relapse outcomes and may speak to this score's utility as a dynamic measure of disease risk in patients exposed to multiple lines and therapy. Conclusions Our report reinforces that CD34+ selected alloHCT can achieve prolonged disease control and long term survival in high risk, heavily treated refractory MM populations, and newly describes certain pre-transplant variables that may help identify patients with better potential survival and relapse outcomes. Given the dismal prognosis and lack of established alternate therapies for RRMM patients, we advocate that identification of favorable or adverse pre-transplant variables during pre-alloHCT assessment be used to inform alloHCT decision-making rather than to exclude certain patient cohorts from this potentially effective and curative treatment option. Disclosures Perales: Abbvie: Other: Personal fees; Merck: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Takeda: Other: Personal fees; Novartis: Other: Personal fees.

Pharmacokinetically Targeted Intravenous Busulfan Combined with Fludarabine (BuFlu) as Conditioning Prior to Allogeneic Peripheral Blood Hematopoietic Cell Transplant: Pretransplant Predictors of Outcomes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3347-3347
Author(s):  
Janelle Perkins ◽  
Jongphil Kim ◽  
Claudio Anasetti ◽  
Mohamed A Kharfan-Dabaja ◽  
Ernesto Ayala ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Disease Risk ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Increased Risk ◽  
Multivariable Analyses ◽  
Standard Risk ◽  
Risk Of Relapse

Abstract Abstract 3347 Poster Board III-235 We report here our experience with 145 consecutive patients (pts) treated with IV busulfan and fludarabine (BuFlu) as conditioning prior to allogeneic hematopoietic cell transplant (HCT). Bu was dosed at 130mg/m2/day on days 1 and 2 with pharmacokinetic (PK) targeting for days 3 and 4; the dose of Flu was 40mg/m2/day for 4 days. The median age was 48 (range 22-68) years. Median HCT Comorbidity Index (HCT-CI) was 3 (range 0-9) and median Karnofsky performance status (KPS) was 100% (60-100%). Sixty-two pts received grafts from HLA matched siblings, 61 from matched unrelated donors (MUD), and 22 from 1 antigen/allele mismatched MUD (mMUD). Disease status was categorized in 50 pts as standard risk (acute leukemia in CR1 or CML in CP1) and in 91 pts as high risk (including acute leukemias > CR1, CML.>.CP1, MDS, MPD, lymphoma, myeloma, and CLL). 4 pts had aplastic anemia. Bu doses were targeted to a daily area under the concentration time curve (AUC) value of 5300 uM*min. Median actual AUC after the first dose was 5002 uM*min (range 3609-8190 uM*min) and doses 3 and 4 were adjusted in 92 pts (63%) to achieve the overall target AUC. Median total Bu dose to achieve AUC target was 520 mg/m2 (range 332-1040 mg/m2). Median Bu clearance (Cl) was 2.7 ml/min/kg (range 1.5-5.2 ml/min/kg). Maximum Bu concentrations (Cmax) after the first dose was 3315 ng/ml (range 1135-4848 ng/ml). First dose Bu AUC, Cmax, and Cl were not correlated with age, race, ethnicity, KPS, or HCT-CI. Women had significantly higher Cl than men (median 2.9 vs 2.6 ml/min/kg; p=0.001). Grade 3 or 4 elevations in hepatic transaminases occurred in 15 pts (10%), hepatic VOD/SOS in 6 pts (4%), and interstitial pneumonitis in 4 pts (3%). None of these toxicities were associated with any of the PK parameters measured. 100 day and 1 year non-relapse mortality (NRM) were 7% and 23% respectively. In multivariable analyses, neither first dose Bu AUC nor Bu Cl were associated with NRM. Having an unrelated donor (MUD: HR 2.68; p=0.025 and mMUD: HR 3.64; p=0.009) and a diagnosis of CML (HR 3.82; p<0.001) or lymphoma (HR 5.15; p=0.005) were associated with increased NRM. In multivariable analyses of relapse, only first dose AUC was significantly associated, with >6000 uM*min predictive of an increased risk of relapse (HR 2.66; p=0.007). The only significant predictor of overall and progression-free survival in multivariable analysis was disease risk. Overall and progression -free survivals at 2 years for the standard risk vs high risk groups were 61% and 57% vs 39% and 32% (p=0.04 and p=0.03, respectively). The increased risk of relapse in the high first dose AUC group may be related to an association between Bu Cl and uptake into malignant cells or the presence of a larger proportion of patients in this group with high risk features other than the predefined disease risk. We conclude that PK targeting of Bu provides a safe method of delivering high doses given that increased toxicity and NRM were not seen in pts with high first dose AUC due to dose adjustment. Disclosures: Perkins: PDL BioPharma: Research Funding. Off Label Use: IV Busulfan and Fludarabine for pre-transplant conditioning. Fernandez:Otsuka: Consultancy. Field:PDL BioPharma: Research Funding.

High Cytogenetic or Molecular Genetic Risk Acute Myeloid Leukemia

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 474-480 ◽  
Author(s):  
Elihu Estey
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell ◽  
Remission Induction ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Npm1 Mutation ◽  
Monosomal Karyotype ◽  
Acute Myeloid

Abstract Resistance, manifested as failure to enter remission despite living long enough to do so or as relapse from remission, is the principal cause of therapeutic failure in acute myeloid leukemia, even in patients age ≥ 75. Recently, a “monosomal karyotype” in acute myeloid leukemia blasts has been found to be a principal predictor of resistance. It is also clear that patients with a normal karyotype, and other intermediate prognosis karyotypes, can be placed into a high-risk group based on the absence of a mutation in the NPM1 gene or the presence of an internal tandem duplication (ITD) of the Fms-like tyrosine kinase 3 gene (FLT3) gene, particularly if there is loss of the wild-type FLT3 allele. The effects of other genetic abnormalities have been inconsistent, perhaps reflecting differences in expression of the abnormality and its translation into protein. Several reports have shown the prognostic potential of profiling global gene expression, micro-RNA expression, DNA methylation, and proteomics. Although routine application of these approaches is still premature, pretreatment assessment of the nucleophosmin 1 (NPM1) mutation and FLT3 ITD status, as well as cytogenetics, should be routine. These results can be used to guide the choice of remission induction therapy, for example, by placing patients with monosomal karyotype or FLT3 ITDs on clinical trials. Allogeneic hematopoietic cell transplant in first complete remission is generally indicated for high-risk patients. However, new approaches are needed to reduce the high rates of relapse, even after hematopoietic cell transplant.

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