Allogeneic Stem Cell Transplantation (SCT) for Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) in Elderly Patients (Older than 60 Years)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2025-2025
Author(s):  
Michele Pohlen ◽  
Christoph Groth ◽  
Tim Sauer ◽  
Dennis Görlich ◽  
Rolf Mesters ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Treatment Outcomes ◽  
Cell Transplantation ◽  
Older Patients ◽  
Conventional Treatment ◽  
Advanced Disease ◽  
Disease Status ◽  
Risk Models ◽  
The Impact

Abstract Allogeneic SCT is the most potent post-remission therapy for AML patients, particularly in patients aged >40-45 years, and the only curative option for patients with refractory AML or with high-risk MDS. Although median age at diagnosis is above 65 years for both entities, for patients aged 60 years or older, studies evaluating allogeneic SCT as post-remission therapy or as salvage therapy are limited. Dose adapted / reduced conditioning for patients in remission and sequential conditioning (intensive chemotherapy followed by dose adapted conditioning), for patients with active leukemia / high-risk disease, together with improvement in supportive care, have shown improved outcome results for SCT in younger and older patients. Aiming to predict treatment outcomes of patients undergoing allogeneic SCT, various transplant specific risk models have been introduced in the past. Assuming that these risk models might be of value especially in older patients, we performed a retrospective single center analysis of transplanted patients, incorporating the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), the European Group for Blood and Marrow Transplantation (EBMT) Score and the Disease Risk Index (DRI). Between 1999 and 2014, 187 patients (pts) with AML (87%) or MDS (13%) aged ≥60 years (median age of 64 years, range 60 - 77 years) received an allogeneic SCT at our institution, either from a HLA-identical related (50 pts.), HLA-matched unrelated (103 pts.), or an HLA-mismatched donor (34 pts). Median follow-up of surviving patients was 36 months (range 1 to 173 months). All patients with AML received a cytarabine-based standard induction therapy. Conditioning prior to transplant consisted of dose reduced / dose adapted therapy (TBI-, busulfan- or treosulfan-based) or sequential conditioning (for patients with high risk or refractory disease). Thirty-nine of the 47 AML patients transplanted in first complete remission (CR1) had a high-risk AML, defined by an adverse cytogenetic risk profile (16 pts), persisting AML after first induction therapy (12 pts), a secondary AML (6 pts.), or persisting / increasing minimal residual disease (5 pts). MDS patients had mainly an advanced disease with blast count 10-19% (19/24 pts). For all patients, an overall survival (OS) at 3 years of 35% (95% CI: 27-42%) was observed. Cumulative incidences of NRM and relapse at one year were 37% and 22%, respectively. Patients transplanted in CR1 showed a 3-year OS of 49%, whereas patients transplanted in subsequent remission, with active AML, or high-risk MDS had a 3-year OS of 26%, 28% and 31%, respectively. Univariate analysis of the whole group showed that advanced and/or active disease (advanced/active AML/MDS vs. AML CR1, p = .04), high DRI (high/very high vs. low/intermediate, p = .06), and poor Eastern Cooperative Oncology Group Score (ECOG; ≥2 vs. 0 or 1, p=.0001), were associated with an inferior OS. Patient age had no impact on outcome parameters. In a multivariate analysis of disease / transplant related risk factors (status pre transplant, EBMT-score, HCT-CI and DRI) only disease status pre transplant was an independent prognostic factor for OS (active / advanced disease vs. CR1, hazard ratio 1.55; 95% CI 1.01-2.38). These results indicate that patient's age ≥60 years in general is no limiting factor for an allogeneic transplant, even if refractory to conventional treatment. Pre-transplant selection of patients eligible for intensive treatment was most likely one relevant bias in our analysis, limiting the determination of the impact of preexisting comorbidities on treatment outcomes. Given the prognostic impact of the disease status at transplant, the improvement of transplant results in elderly patients, and the dismal prognosis of older patients with myeloid neoplasms receiving conventional treatment, the impact of allogeneic SCT, especially in early disease stages / CR1 of patients with MDS / AML eligible for intensive treatment has to be further studied in prospective trials. Disclosures No relevant conflicts of interest to declare.

Comparable Outcome after Allogeneic Hematopoietic Cell Transplantation from Matched Unrelated and Sibling Donors in Elderly Patients with Acute Myeloid Leukemia - Results of a Retrospective Analysis in 368 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 172-172 ◽  
Author(s):  
Johannes Schetelig ◽  
Martin Bornhäuser ◽  
Christoph Schmid ◽  
Bernd Hertenstein ◽  
Rainer Schwerdtfeger ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Disease Status ◽  
Allogeneic Hct ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
Acute Myeloid

Abstract Purpose: In patients with acute myeloid leukemia (AML) differential indications for matched sibling and unrelated hematopoietic stem cell transplantation (HCT) are considered and arbitrary age limits for HCT exist. We sought to determine whether donor type is a prognostic factor in elderly patients in the era of high-resolution DNA-based HLA-typing. Patients and Methods: We performed a retrospective cohort analysis in patients with AML older than 50 years who had received an allogeneic HCT between 1995 and 2005. If available, DNA from donors and recipients of unrelated HCT was used for molecular retyping in order to get information on HLA-A, -B, -C, -DRB1 and DQB1 at the allele-level. Donor-recipient pairs with fully matched donors or one mismatch out of ten alleles were considered well-matched. Results: We identified 368 patients with cytogenetic intermediate or high risk AML who fulfilled the entry criteria. The median age of this cohort of patients was 57 years (range 50 to 73 years). 46% of patients had matched sibling donors, 3% related non-sibling donors, 41% well-matched unrelated donors and 10% poorly matched unrelated donors. In the respective period the percentage of patients with unrelated donors increased from 0% in 1995 to 64% in 2004. High risk features were a history of prior myelodyplasia in 34% of patients, poor risk cytogenetic abnormalities in 33% of patients and a disease status beyond CR1 in 62% of patients. 72% of patients received reduced-intensity conditioning regimens. Peripheral blood stem cells were used as graft in 84% of patients. In multivariate analysis disease status at HCT (p<0.001) and cytogenetic risk (p<0.001) proved to be highly significant predictors, both, for EFS and OS. Whereas, the relative risk of a patient with a well-matched unrelated donor compared to a sibling donor was 0.9 (95% CI, 0.6 to 1.2) for EFS and 1.0 (95% CI, 0.7 to 1.4) for OS. In subgroup analyses EFS was better in AML patients with cytogenetic high risk disease beyond first remission (CR1) (p=0.0147) who had well-matched unrelated donors compared to those with sibling donors and not inferior in any of the other subgroups. Conclusions: Allogeneic HCT from matched unrelated donors (>=9/10) should be considered equivalent to sibling HCT in terms of survival for patients above the age of 50 years with intermediate or high risk AML. In advanced stages of AML with high risk cytogenetics patients with matched unrelated donors may even have better EFS compared to those with sibling donors.

scholarly journals The Impact of Age on the Outcome of Primary Treatment for Classical Hodgkin's Lymphoma: 70 Years of Age Is a Clinical Relevant Cutpoint and the Most Important Predictor of Overall Survival

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1559-1559
Author(s):  
Lourdes Calvente ◽  
Manjula Maganti ◽  
Mary Gospodarowicz ◽  
David C. Hodgson ◽  
Danielle Rodin ◽  
...  
Keyword(s):  
High Risk ◽  
Febrile Neutropenia ◽  
Treatment Outcomes ◽  
Older Patients ◽  
Research Funding ◽  
Multivariable Analysis ◽  
Advanced Stage ◽  
Age Group ◽  
Grade 3 ◽  
The Impact

Introduction: Classical Hodgkin lymphoma (cHL) typically affects younger patients but 15-35% are >60 years. The age used to define an elderly population has varied but age 60 is frequently used. A clinically relevant definition of older age could be based on the use of alternate treatments due to different efficacy and/or toxicity. Treatment outcomes may also be influenced by tumor biology and patient comorbidity that vary with age. We evaluated the effect of age on treatment outcomes in cHL. Methods: All cHL patients treated at our centre between Jan 1999 and Dec 2015 were retrospectively analyzed. Clinical data were obtained from prospectively collected Lymphoma database and additional data was manually retrieved. Treatment for localized disease was combined modality (2-4 cycles of ABVD and potentially 6 cycles for bulk disease > 10 cm; radiation doses 20-35 Gy) with advanced disease typically receiving chemotherapy alone (ABVD 6-8 cycles). Older patients received individualized treatment. We used the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), (Sorror Blood 2005) as the elements can be abstracted retrospectively. Results: 607 patients were identified; 14% were >60 years and 6% were age >70. Baseline characteristics are outlined in table 1. Patients >70 presented more frequently with high-risk HCT-CI and worse ECOG PS. Patients > 60 presented more frequently with advanced stage (61-70 age group: 40%; >70 years: 46%). 65% of the patients age >70 presented with an IPS of >3. Chemotherapy alone approaches were used more commonly in older patients (age 61-70: 40%; age 70+: 51%) than in those <60 years (25%). Within the whole cohort 12 patients received non-anthracycline based treatment (<60: n=4; 61-70: n=1; and >70: n=7).For patients <60 and >70 this decision was made due to prior comorbidities that precluded the use of standard treatment, and for the patient in the 61-70 was because of acute toxicity with ABVD-based chemotherapy. Treatment was discontinued in 33% of the patients > 70 (77% due to toxicity), 21% in the 61-70 years group (30% toxicity) and 6% in patients <60 (29% toxicity). Patients > 70 had higher rates of grade 3-5 febrile neutropenia (28% versus 15% [age 61-70] and 7% [age <60]). Bleomycin toxicity was more common in older patients (age >70: grade 3-4 events 12% of the patients with discontinuation in 66%; age 61-70: 13% with discontinuation rate of 20%) compared to a 1% rate of grade 3-5 events in age <60. There was a grade 5 episode of febrile neutropenia in >70 group and 1 death related to bleomycin in age <60. With a median follow up of 8.6 years, the 10-year OS and PFS were 80.5% and 71.2%, respectively. By age-group, the 10-year OS was 88% (<60 years), 57% (61-70 years) and 15% (age >70 years); (p<0.001) (Figure 1a-b). In multivariable analysis for OS, age 61-70 (HR 2.44, p=0.002) and age >70 (HR 5.72, p=0.001), non-anthracycline based chemotherapy (HR 3.69, p<0.001), high-risk HCT-CI (HR 3.03, p=0.001) and ECOG 2-4 (HR 1.8, p=0.017), were significant. Age >70, type of chemotherapy, high-risk HCT-CI, and advanced stage were significant for PFS in the multivariable analysis (Table 2a-b). Death due to disease or toxicity at 10 years was 13.6% (age <60: 9.7%, 61-70 years: 23.2%; and for age > 70: 50.7%; [p=<0.001]) (Figure 2a-b). Multivariable analysis for cause-specific survival identified age >70 years (HR 4.04, p=<0.001), extranodal disease (HR 2.57, p=0.001) and ECOG 2-4 (HR 2.10, p=0.010) as significant predictors(Table 3). Conclusions: Age >70 years is a clinically relevant age cutoff as it has additional prognostic significance and greater rates of treatment discontinuation and toxicity compared to age 60. The HCT-CI is a useful predictor of outcome in cHL and should be validated prospectively. In multivariable analysis, age, type of treatment, comorbidity and ECOG performance status are independent predictors of OS. Further studies are ongoing to validate these findings and assess biologic differences in older versus younger cHL patients. Disclosures Tsang: Nordic Nanovector: Research Funding. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Kuruvilla:Janssen: Research Funding; Roche: Honoraria; Novartis: Honoraria; Merck: Honoraria; Gilead: Honoraria; Seattle Genetics: Consultancy; Roche: Consultancy; Merck: Consultancy; Karyopharm: Consultancy; Celgene: Honoraria; BMS: Honoraria; BMS: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Astra Zeneca: Honoraria; Janssen: Honoraria; Roche: Research Funding; Amgen: Honoraria; Seattle Genetics: Honoraria; Karyopharm: Honoraria.

Risk Factors for Outcomes of Family Haploidentical Allogeneic Stem Cell Transplantation for Adults with Acute Leukemias: A Survey on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2146-2146
Author(s):  
Fabio Ciceri ◽  
Myriam Labopin ◽  
Vanderson Rocha ◽  
Jacob M. Rowe ◽  
Donald Bunjes ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Advanced Disease ◽  
Disease Status ◽  
Acute Leukemias ◽  
Factors Associated

Abstract Results of family haploidentical allogeneic stem cell transplantation (Haplo-SCT) have been reported from single-center studies as a curative treatment option for patients with high risk acute leukemias. We analysed 273 adult patients with de novo acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) receiving an Haplo-SCT transplanted from 1995 to 2002 in 75 EBMT centers. Overall, 170 AML patients underwent transplantation in CR1 (n=39), CR2 (n=34) or in advanced disease (n=97); median age was 38y (16–70). Overall, 103 ALL patients underwent transplantation in CR1 (n=31), CR2 (n=22) or in advanced disease (n=50); median age was 26y (16–56). Graft composition was based on CD34+ cell selection of PBSC, with median CD34+ cells x106/kg of 7.3 (1.1–45.5) in AML and 8.3 (1.14–30) in ALL. Conditioning regimen was TBI-based in 69% and 87% in AML and ALL respectively. Primary engraftment was documented in 87% AML and in 83% of ALL patients, with ANC 0.5 x109/L in a median of 13 days (8–35) and a 2y probability of PLT > 50 x109/L of 80+/− 5%. The use of TBI was significantly associated with engraftment (90% vs 71%) when adjusting for CD34 dose. The cumulative incidence of acute GvHD >=II was 16% in AML and 15% in ALL. With a median follow-up of 19 months (1–85), the estimated leukemia-free survival (LFS) at 2 years in AML was 39±9%, 33 ±10% and 4±3% and in ALL was 28±9%, 16±8, and 0% for CR1, CR2 and advanced patients respectively. Cumulative incidence using competing risks, for relapse (RI) at 2 y in AML was 8 ±8%, 9 ±9%, 25±8% for CR1, CR2 and advanced; RI in ALL was 27±16% and 41 ±20% in CR1 and CR2. The non-relapse mortality (NRM) at 2 y in AML was 52±18%, 56 ±19%, 69±8% for CR1, CR2 and advanced patients; NRM in ALL was 44±18% and 41±21% in CR1 and CR2. In a multivariate analysis for LFS, advanced disease status at transplant (RR 0.4), ALL (RR 0.5), recipient’s age >33 years (RR 0.4), and absence of TBI in conditioning (RR 0.6) were factors associated with lower LFS. Factors associated with higher transplant-mortality were advanced disease status (RR 2.01), absence of TBI (RR 1.6) and year of transplant<2000 (RR 1.42). Predictive factors for RI were diagnosis of ALL (RR 2.39) and advanced disease (RR 1.96). In conclusion, outcomes of allogeneic transplantation from haploidentical family donors in adults with high risk acute leukaemia are promising and should be considered in the algorithm treatment for patients with an indication of allogeneic SCT lacking an HLA identical donor. Status of the disease, age, type of leukemia and conditioning are some factors associated with outcomes after Haplo-SCT.

Intravenous Busulfan-Based Conditioning Prior to Allogeneic Stem Cell Transplantation in Adults Patients with AML - An ALWP-EBMT Survey.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1995-1995 ◽  
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Avichai Shimoni ◽  
Donald Bunjes ◽  
Pedro Pimentel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Advanced Disease ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
The Impact

Abstract Oral Busulfan (Bu) is the historical backbone of pre-allogeneic stem cell transplantation (alloSCT) conditioning regimen. However, oral Bu has an erratic and unpredictable absorption with wide inter and also intra-patient (pt) variability. In contrast, I.V. Busulfan (IV Bu) is with more predictable pharmacokinetics and favorable toxicity profile. In order to assess the impact of the use of IV Bu, the ALWP of the EBMT performed a survey in AML pts who received IV-Bu as part of their pre-alloSCT conditioning regimen. 36 EBMT centers participated in this study: 9 centers performed more than 10 transplants each. Overall, 271 alloSCT were analyzed. Age was 44 (range, 16–67) years. 146 were males (54%) and 125 (46%) were females. Disease status at alloSCT was CR1-53%, CR2-16%, primary refractory-13%, Rel1-12%, Rel2-5% and untreated-1%.77% of the pts were with intermediate, 15% with poor and 8% with good risk cytogenetics, respectively. Median WBC at diagnosis was 26×109/L. Conditioning consisted of IV Bu and cyclophosphamide (IV BuCy) in 52%, IV Bu and fludarabine (IV BuFlu) in 38% and various other IV Bu containing regimens in 10% of the pts, respectively. Overall, conditioning was myeloablative in 80% and reduced-intensity (RIC) in 20% of the alloSCT, respectively. Donors were: identical siblings-59%, matched unrelated-28%, mismatched unrelated-10%, mismatched family donors-2%, syngeneic 1%. 83% of the pts were transplanted with mobilized PBSC grafts while 17% received BM grafts. GVHD prophylaxis consisted of CSA and MTX in 85% of the transplants. With median follow up of 24 (range, 1–66) months, 53% of the pts are alive while 47% have died. Day 100 mortality was 7%. The incidence of veno-occlusive disease of the liver (VOD) was 10.4%. VOD was more frequent in pts that were transplanted from unrelated donors in comparison to those who were transplanted from sibling donors (18% vs. 5%, respectively). It was also more common after myeloablative conditioning than RIC (11.5% vs. 5.5%, respectively). Median age of pts with VOD was 42(17–65) years, not different than the age of the whole group, but they had more advanced disease (primary refrectory-35%, Rel2-30%). Day of onset of VOD was +10(range, 1–162). VOD was severe in only 15% of the pts and only 6 pts died of VOD. All together 30% of the pts with VOD are alive. Overall, alloSCT transplant related mortality (TRM) was 22±4% for pts transplanted at CR1 vs 33±8% for pts transplanted at advanced disease. Similarly, leukemia free survival (LFS) for pts transplanted at CR1 was 55±4% vs. 21+5% for pts transplanted in advanced disease. In summary, IV Bu based conditioning reduced the incidence and severity of VOD post alloSCT for AML as compared to published figures for historical controls. A randomized trial assessing VOD incidence and TRM using IV BuCy vs. IV BuFlu with 2 vs. 4 days of IV Bu, respectively may be indicated.

Outcome of Patients Aged ≥60 After Allogeneic Hematopoietec Cell Transplantation: Age Has No Impact on Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3540-3540 ◽  
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang A. Bethge
Keyword(s):  
High Risk ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Performance Status ◽  
Chronic Gvhd ◽  
Allogeneic Hct ◽  
Kaplan Meier ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Abstract 3540 Historically, allogeneic hematopoietic cell transplantation (HCT) has been offered only to patients with good performance status and below the age of 60. However, the peak incidence of most hematologic malignancies is above 60 years of age. The introduction of reduced intensity conditioning (RIC) regimens enabled successful allogeneic HCT in patients with considerable comorbidities and older than 60 years. The impact of age on outcome of allogeneic HCT in patients ≥60 years has not been evaluated extensively. We retrospectively analyzed 109 consecutive patients (f=43, m=66) aged≥60 who received allogeneic HCT 2000–2010 at our institution. Median age of the patients was 65 years (range, 60–76). Patients were grouped in two cohorts depending on age: group 1 aged 60–65 years (n=60, median age=63) and group 2 aged 66–76 years (n=49, median age=68). Diagnoses were acute leukemia (AML n=65, ALL n=1), myelodysplastic syndrome (n=14), osteomyelofibrosis (n=7), non-Hodgkin lymphoma (n=9), multiple myeloma (n=8), aplastic anemia (n=1), chronic myeloid leukemia (n=2) and chronic lymphatic leukemia (n=2). At time of HCT, 41 of the patients were in complete remission (CR), 68 in partial remission (PR) (group 1: CR 21, PR 39; group 2: CR 20, PR 29) and 18 patients had a preceding HCT, 14 in group 1. Conditioning regimens were grouped in high (TBI/Bu+Cy, n=5, all group 1), intermediate (FLAMSA, Flu/Mel/BCNU, n=28, group 1=11, group 2=17), low (FLU+alkylans, n=48, group 1=32, group 2=16) and minimal (2GyTBI/Flu, n=28, group 1=12, group 2=16) intensity. Intermediate intensity conditioning was particularly used for high risk patients in PR (25/28). 22 patients were transplanted from matched related (MRD), 46 from matched unrelated (MUD) and 41 from mismatched unrelated donors (MMUD). Kaplan-Meier-estimated 3-year overall survival (OS) was 45% for all patients, 32% for group 1 and 62%, for group 2, respectively (p=0.02), with more patients with high risk constellation in group 1. 3-year OS for patients transplanted with MUD was 57%, with MMUD 46% vs. with MRD 0% (p=0.01). Non-relapse-mortality was 28% for all patients, 40% in group 1 and 12% in group 2, probably due to the higher intensity in conditioning in group 1. The outcomes with intermediate, low and minimal intensity conditioning were comparable, while all patients after high intensity conditioning died. Table 1 describes Kaplan-Meier estimated 3-year-OS and statistical univariate analysis by log-rank test in the different subgroups. Table 1. 3-year OS (in%) All Group 1 Age 60–65 Group 2 Age 66–76 Remission CR 52 p=0.25 31 p=0.76 77 p=0.15 PR 40 32 50 Conditioning high 0 p=0.5 0 p=0.08 – p=0.38 intermediate 52 50 53 low 48 43 57 minimal 45 17 67 Donor MRD 0 p=0.01 0 p=0.06 73 p=0.45 MUD 57 53 65 MMUD 46 40 33 GVHD acute no 18 p=0.003 13 p=0.008 33 p=0.27 ≥II 43 53 58 chronic no 39 p=0.25 36 p=0.70 52 p=0.08 limited 52 30 100 extensive 50 30 67 In group 1 the outcome of minimal conditioning was inferior compared to intermediate and low conditioning while patients in group 2 had a better outcome with minimal vs. low and intermediate conditioning. Incidences of acute GVHD ≥II, limited and extensive chronic GVHD (cGVHD) were 10%, 28% and 13%, respectively. In group 1, acute GVHD ≥II occurred in 13% and cGVHD in 35%, in group 2 in 5% and 41% of the patients, respectively. Acute GVHD ≥II was associated with inferior outcome (3-year OS of 18% vs. 43%, p=0.003) while cGVHD had a positive impact on OS. In group 2 patients with limited cGVHD showed better 3-year OS than patients without cGVHD (67% vs. 52%, p=0.12). Age alone had no major impact on outcome of allogeneic HCT. Patients aged ≥60 seemed to benefit from the use of MUD rather than an older MRD. Chronic GVHD had a positive influence on survival. Our data indicate that the regimen used should be tailored to disease risk and patient performance status. Disclosures: No relevant conflicts of interest to declare.

Fludarabine and Targeted Busulfan Is Safe and Effective Conditioning Before Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 891-891
Author(s):  
Ghada M Kunter ◽  
Janelle Perkins ◽  
Lia Perez ◽  
Joseph Pidala ◽  
Teresa Field ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Unrelated Donor ◽  
Risk Of Relapse

Abstract Abstract 891 Background: Chemotherapy for adult patients with acute lymphoblastic leukemia (ALL) is associated with high risk of relapse and an overall 2-year survival of 40 to 50%. Allogenic hematopoietic cell transplantation (HCT) in first complete remission (CR1) decreases the risk of relapse and improves outcome over chemotherapy for adult ALL pts, but non-relapse mortality (NRM) is a drawback especially in older patients. In the MRC UKALL XII/ECOG E2993 trial, the 2 year NRM of patient with an allogenic donor was 19% in standard risk patients and 36% in patients over 35 years or those with high risk leukemia. We tested safety and efficacy of a non-irradiation regimen consisting of fludarabine (FLU) and pharmacokinetically-targeted busulfan (BU) for adults with ALL in CR1. Methods: We report the outcomes of 42 consecutive patients with ALL in CR1, 21 positive for the Philadelphia chromosome (Ph+). All patients were in complete morphologic remission before HCT. The median age was 33 (range: 19–62) years, 19 were females and 23 males. Median time from diagnosis to HCT was 6 (range: 3–45) months. Thirty patients were treated to achieve an average daily BU area under the curve (AUC) of 5300 microM-min for 4 days, and 12 patients were treated on a clinical trial to achieve an average daily BU AUC of 6000 to 7500 microM-min for 4 days. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus in all patients, in combination with either methotrexate (88%) or sirolimus (12%). Twenty (48%) patients received grafts from matched related donor, 16 (38%) from matched unrelated donor and 6 (14%) from a mismatched unrelated donor. The median follow-up of surviving patients is 2 (median 1.2–4.3) years. Results: Overall survival at 2 years was 66% (95% CI 52%–81%) for all patients, 70% (95% CI 51%–88%) for Ph- and 63% (95% CI 41%–85%) for Ph+ patients (p=0.59). Overall survival did not differ by age, above or below 35 years (p=0.39). Disease-free survival at 2 years was 59% (95% CI 44%–74%) for all patients, 65% (95% CI 45%–84%) for Ph- and 52% (95% CI 28%–74%) for Ph+ pts (p=0.49). The cumulative incidence of relapse at 2-year was 27% (95% CI 16%–45%). The cumulative incidence of acute GVHD grades II–IV was 64% (95% CI 51%–81%) and grades III–IV GVHD was 25% (95% CI 13%–47%). The cumulative incidence of non-relapse mortality (NRM) was 5% (95% CI 1%–18%) at 100 days and 14% (95% CI 7%–30%) at 2 years. Conclusions: These data show that FLU with myeloablative doses of PK targeted BU is an effective alternative to total body irradiation and etoposide or cyclophosphamide for conditioning patients with ALL without an increased risk of relapse after HCT. The low NRM allows to safely delivering myeloablative chemotherapy and allogenic HCT to older patients. This HCT regimen should be prospectively compared to chemotherapy for adult patients with ALL. Disclosures: No relevant conflicts of interest to declare.

Statins Use Improves the Clinical Outcomes of Salvage Therapy in Relapsed/Refractory CLL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3931-3931
Author(s):  
Long Xuan Trinh ◽  
Young Kwang Chae ◽  
Preetesh Jain ◽  
Ohad Benjamini ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Salvage Therapy ◽  
Older Patients ◽  
Conflicts Of Interest ◽  
Young Patients ◽  
The Other ◽  
Concurrent Use ◽  
The Impact

Abstract Abstract 3931 Introduction - Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase. In addition, statins possess anti-inflammatory, immunomodulatory, antioxidant, and cell growth inhibitory properties. In B- CLL cells, statins induce in-vitro apoptosis (Daphne Chapman-Shimshon et-al), suggesting that statins might possess properties. We noticed a high prevalence of dyslipidemia in patients with chronic lymphocytic leukemia (CLL). However the impact of dyslipidemia and its modulation by statins on clinical outcomes of patients with CLL remains unclear. Therefore, we conducted a retrospective analysis to assess the effect of statins in patients with CLL who received salvage (fludarabine, cyclophosphamide and rituximab) FCR chemotherapy. Methods - We analyzed the clinical outcome of relapsed/refractory patients with CLL (n=284) who underwent FCR salvage therapy at our institution between 1999 and 2012. Patients who were uninterruptedly treated with statins at least one month prior to and during salvage therapy (n=35) were assigned to the statins arm, whereas the other arm consisted of 249 patients who were not treated with statins. The Cox proportional hazards regression model was used to assess the association between patient characteristics and progression-free survival (PFS) and overall survival (OS). Actual survival and PFS were estimated using the method of Kaplan-Meier, and OS and PFS were compared among two groups of patients using log-rank test. Results - All pretreatment characteristics of the patients with concurrent use of statins were similar to those who were not treated with statins except for their age. Patients in the statins arm were older: 21 patients (60%) were older than 65 compared to 74 patients of 249 (30%) in the other group (p<0.05). The median OS and PFS of all 284 patients were 3.9 years (95% CI: 3.4–4.5) and 1.74 years (95% CI: 1.6–2.3), respectively. PFS was significantly longer in patients treated with statins. Fifteen of the 35 statin-treated patients (43%) as opposed to only 36 of 249 (14%) in the non-statins group experience no disease progression. Concurrent use of statins significantly prolonged PFS. The median PFS for statin-treated v/s. untreated was 4.6 and 1.7 years, respectively (p<0.05). This significantly improved PFS was consistent in young and elderly patients. In young patients (age < 65) with statins, the median PFS was not reached whereas in patients who were not treated with statins it was 2 years (p<0.05). In older patients (age ≥ 65), PFS was significant longer with concurrent use of statins than without statins; estimated PFS were 2 and 1.6 years, respectively (p<0.05). With the median follow-up of 5 years, the median overall survival was significantly longer in patients treated with statins, with 17 of 35 (49%) patients of the statins group and 59 (24%) of 249 in patients who were not treated with statins alive at the end of study. Concurrent use of statins significantly prolonged OS with an estimated median OS for the two groups of 6.9 years and 3.9 years, respectively (p<0.05). This significantly improved OS was consistent in young and elderly patients. Young patients (age <65) with statins had a significant prolonged survival with an estimated OS of 8.6 years whereas estimated OS in young patients without statins (p<0.05) was only 4 years. In older patients (age ≥65) the median OS was significantly longer with the concurrent use of statins than without statins; estimated OS in the two subgroups were 6.9 and 2.6 years respectively, (p<0.05). Conclusions - In conclusion, concurrent use of statins significantly improved OS, PFS in relapsed/refractory CLL patients treated with salvage FCR therapy. Further studies to determine the role of statins and mechanism of action in patients with CLL are warranted. Disclosures: No relevant conflicts of interest to declare.

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