Gene Expression Profiling Predicts Clinical Outcomes in Newly Diagnosed Multiple Myeloma Patients in a Standard of Care Setting

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5628-5628 ◽  
Author(s):  
Catherine M Claussen ◽  
Hans Lee ◽  
Jatin J. Shah ◽  
Tiffany Richards ◽  
Nina Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Outcomes ◽  
Expression Profiling ◽  
Care Setting ◽  
Standard Of Care ◽  
Gene Gain ◽  
Time To Event ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Patient Groups

Abstract Introduction: Multiple Myeloma is a heterogeneous cancer that affects the bone marrow. Given this heterogeneity, we aimed to elucidate the role of gene expression profiling (GEP) in identifying different MM subtypes and explore their relationship to clinical outcomes in a standard of care setting. Methods: We retrospectively analyzed all NDMM patients with baseline GEP analysis. 55 patients from April 2014 until March 2016 were identified and included in our analysis. GEP was performed using CD138+ cells from bone marrow samples through MyPRS® (Signal Genetics, Little Rock, AR). Fisher's exact test was used to evaluate the associations between two categorical variables. The Wilcoxon rank sum test was used to evaluate the difference in continuous variables between patient groups. Kaplan-Meier method was used to estimate the time to event endpoints including relapse free survival (RFS) and overall survival. The log-rank test was used to evaluate the differences in the time to event endpoints between/among patient groups. Univariate Cox proportional hazards model was used to evaluate the association between a continuous variable and relapse free survival. Results: Median age was 61 (38-76). Patients presented with lytic lesions (80%), anemia (78%), kidney dysfunction (24%) and hypercalcemia (31%). One patient did not meet CRAB criteria, but had 60% plasma cells in the bone marrow and an involved/uninvolved sFLC ratio of 199. All patients were treated with bortezomib (88%) or carfilzomib (12%) initial therapy in combination with lenalidomide (83%) or cyclophosphamide (17%). All patients received triple therapy as initial treatment, with 60% of patients receiving an upfront autologous transplant. With median follow-up of 12 months (1.64-24.54 months) 75% of patients had not relapsed and median overall survival had not been reached. 13 (24%) patients were characterized as high risk (HR) by GEP. GEP risk category predicted RFS (p=0.0014) in this series of patients (Fig. 1). Table 1 shows GEP risk subtypes with clinical outcomes and association to FISH abnormalities. We previously reported that HR FISH abnormalities are present in GEP low risk (LR) patients. LR GEP patients with CKS1B gene gain by FISH (n=9, 23%) had 100% RFS at 21 months, while 60% of HR GEP patients with CKS1B gene gain had relapsed by 24 months (p=0.0297, Fig. 2). All patients with HR GEP and 17p deletion relapsed by 14 months whereas only one patient with LR GEP and 17p deletion died 1 year from diagnosis, with an unknown cause of death (p=0.18, Fig. 3). Conclusion: Cytogenetics and FISH are still the current standard of care to predict prognosis in NDMM, direct care and inclusion in clinical trials. This study in a standard of care setting shows that GEP further refines prognosis in patients with HR FISH abnormalities. Future studies in larger cohorts of patients are warranted to confirm our findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia in remission: prolonged survival associated with acute graft-versus-host disease.

1987 ◽  
Vol 5 (9) ◽  
pp. 1348-1355 ◽  
Author(s):  
D J Weisdorf ◽  
M E Nesbit ◽  
N K Ramsay ◽  
W G Woods ◽  
A I Goldman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Maintenance Chemotherapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Acute Graft

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.

Improved Outcome of Children with Down Syndrome (DS) and High Risk Acute Lymphocytic Leukemia (HR-ALL): A Report of CCG-1961.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 586-586 ◽  
Author(s):  
Caroline Hastings ◽  
James A. Whitlock ◽  
Mei La ◽  
Nita Seibel
Keyword(s):  
Bone Marrow ◽  
Down Syndrome ◽  
Standard Of Care ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Post Induction ◽  
Cancer Group ◽  
Drug Induction ◽  
Grade 3 ◽  
To Receive

Abstract Down syndrome patients with ALL (ALL-DS) have unique clinical and biologic features which can make treatment a challenge particularly in regards to toxicity. In order to evaluate the optimal treatment for ALL-DS with higher risk ALL we compared the outcomes of ALL-DS patients (n=51) enrolled on the Children’s Cancer Group (CCG) 1961 protocol for HR-ALL to those of their non-DS counterparts (n=2001). CCG-1961 was open from November 1996 to May 2002 for patients with ALL age 1–9 years and WBC ≥ 50,000 or age ≥ 10 years with any WBC. Rapid early responders (RER ≤ 25% blasts on day 7 bone marrow after 4 drug induction) were randomized in a 2 × 2 design to receive intensive post-induction intensification therapy (IPII) or standard post-induction intensification therapy (SPII) and 1 or 2 delayed intensification phases. Slow early responders (SER > 25% blasts on day 7 bone marrow) were treated with IPII, and randomized to receive idarubicin or doxorubicin. No up-front therapy modifications were prescribed for DS patients (only for toxicity as per protocol). All DS patients were over 2 years of age. DS patients were more likely to have WBC ≥ 50,000 than non-DS (76% vs 53%) and less likely to have T cell immunophenotype (4% vs 23%), lymphoma syndrome (10% vs 23%) or marked splenomegaly (4% vs 12%) at diagnosis. No differences in gender, race, or extramedullary disease were noted in the DS vs non-DS patients. There were 36 RER DS patients (16 randomized to IPII and 20 SPII) and 16 SER patients. There were 6 deaths in the DS patients: 4 early in induction, 1 in consolidation, and 1 in maintenance. All deaths were associated with toxicity and/or infection and 2 patients had progressive disease. DS patients were more likely to have grade 3–4 stomatitis during intensive treatment phases (15.2% vs 1.8% during induction, 23.1% vs 2.9% during delayed intensification #1). The 5-yr event free survival (EFS) was 69.1% (se 8.4%) for DS patients and 70.4% (se 1.5%) for non-DS patients. The 5-yr overall survival (OS) was equivalent for the two groups: 77.9% (se 7.5%) for DS patients compared to 80.9% (se 1.1%) for non-DS patients. The 5 year death as a first event assessment was 88.2% (se 6.6%) (RHR 2.6) vs 95.5% (se 0.7%) for non-DS patients, consistent with an increased incidence of early toxic deaths in the ALL-DS cohort. IPII therapy for RER DS patients resulted in excellent disease control (0 BM relapses vs 5 with SPII). The 4-yr EFS for the IPII DS patients (RER + SER) was 83.7% (se 6.7%) vs 78.8% (se 11.5%) for the RER DS randomized group only. This difference may be explained by the single event in the 16 SER patients; however the small number precludes a definitive conclusion. In conclusion, HR patients with ALL-DS treated with IPII therapy on CCG-1961 have similar OS and EFS to non-DS patients. These results compare favorably with those of other studies. The early mortality due to toxicity in the DS population does not result in decreased EFS or OS as compared to the non-DS population. IPII therapy is well tolerated and effective in HR ALL-DS, as evidenced by excellent outcomes in the RER and SER groups, and should be considered a reasonable standard of care for this patient population.

Strong Histone (H4) Acetylation Is Independently Associated with Better Overall Survival in Newly Diagnosed Acute Myeloid Leukemia (AML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4681-4681
Author(s):  
Mazyar Shadman ◽  
Sarah Gibson ◽  
Claudiu Cotta ◽  
Eric D. Hsi ◽  
Edward Copelan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Group ◽  
Hdac Inhibitors ◽  
Nuclear Staining ◽  
Newly Diagnosed ◽  
Histone H4 ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Histone H4 Acetylation ◽  
Acute Myeloid

Abstract Abstract 4681 Background Histone acetylation is a post-translational modification used by proteins to regulate specific chromatin functions. Histone deacetylases (HDACs) play a pivotal role in the pathogenesis of a subset of acute myeloid leukemias (AMLs). HDAC inhibitors are currently being evaluated in clinical trials. We have previously demonstrated an association between increased histone H4 acetylation and increased relapse-free survival (RFS) in patients with newly diagnosed acute lymphocytic leukemia (ALL) (Advani et al., ASH abstract #2798, 2007) and improved overall survival (OS) in ALL patients with first relapse (Advani et al., ASH abstract #1482, 2008). Here, we evaluated the association between histone H4 acetylation with achievement of complete remission (CR) and also with RFS and OS in patients with newly diagnosed AML. Methods In this retrospective cohort study, we assessed H4 acetylation status in bone marrow biopsies of newly diagnosed AML patients at the Cleveland Clinic between the years 2003-2005. Association with CR, RFS and OS was assessed using univariate and multivariate logistic regression and cox-proportional hazard regression models. Variables used in the models included: age and WBC at diagnosis, gender, cytogenetic (CG) risk group, and history of antecedent hematologic disorder (AHD). CG risk group was ascribed per Cancer and Leukemia Group B criteria. B5-fixed bone marrow core biopsies were reviewed for areas of highest blast concentration. Immunohistochemistry was performed for acetyl-H4 (1:200 dilution; polyclonal; Upstate Biotech, Lake Placid, NY) using automated stainers and heat induced epitope retrieval. In each case, five hundred blasts were counted and only strong nuclear staining was classified as positive. Based on the distribution of cell counts, cases were classified as strongly positive if nuclear staining occurred in > 80% of the blasts. Results Eighty-one patients had adequate tissue and clinical data available. We restricted the analysis to sixty patients who received standard induction chemotherapy with cytarabine and an anthracycline. The median age was 58 years (range 20-79) and median WBC was 8.85 × 109/ L (range 0.8-227.9). Seven patients (11.6%) had favorable CG, 41 (68.3%) had intermediate, and 12 (20%) had poor risk CG. Thirty two percent of patients had an AHD. Thirteen patients (21.6%) received an allogeneic bone marrow transplant in first remission. The median follow-up time was 25.5 months (range 2.1-70.6). Forty five patients (75%) achieved CR and the median OS was 12.7 months (range 0.4-70.6). Using the 80% cut-off, 19 patients (31.6%) were positive for H4-acetylation. Histone (H4) acetylation was not associated with achievement of CR (OR=4.1, 95% CI 0.7-24.5, p=0.1) or relapse-free survival (HR 0.62, 95% CI 0.18-2.08, p=0.44). However, in multivariate analysis, histone acetylation was associated with a significantly better OS (HR=0.51, 95% CI 0.29-0.88, p=0.01). Inclusion of allogeneic transplant in the multivariate models did not change these estimates. Conclusion Strongly positive histone (H4) acetylation is associated with better OS in multi-variate analysis. The results mimic our previous findings in ALL patients. Further studies will need to include FLT3 and NPM status in patients with normal cytogenetics in the multi-variate model. These results provide a rationale for AML regimens incorporating HDAC inhibitors, and use of this assay as a potentially relevant biomarker during HDAC inhibitor therapy. Disclosures: No relevant conflicts of interest to declare.

Successful therapy of convoluted T-lymphoblastic lymphoma in the adult

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 92-98
Author(s):  
AM Levine ◽  
SJ Forman ◽  
PR Meyer ◽  
SC Koehler ◽  
H Liebman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Bone Marrow Involvement ◽  
Cranial Irradiation ◽  
Lymphoblastic Lymphoma ◽  
Intrathecal Methotrexate ◽  
Induction Phase ◽  
Relapse Free Survival ◽  
Free Survival ◽  
T Lymphoblastic Lymphoma

Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16–73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

Meta-analyses of studies on bone marrow micrometastases: an independent prognostic impact remains to be substantiated.

1998 ◽  
Vol 16 (2) ◽  
pp. 557-566 ◽  
Author(s):  
I Funke ◽  
W Schraut
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Epithelial Cells ◽  
Tnm Classification ◽  
Effect Estimate ◽  
Prognostic Impact ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Bone Marrow Micrometastases ◽  
Meta Analyses

PURPOSE In 1997, the immunocytologic detection of isolated tumor cells in bone marrow, termed micrometastasis, will be optionally included in the tumor-node-metastasis (TNM) classification indicated M1(i). In the present meta-analyses, 20 studies, which included 2,494 patients, regarding the prognostic influence of a positive bone marrow micrometastases (BMM) status on relapse-free and/or overall survival were analyzed. MATERIALS AND METHODS The literature search included the Medline and Current Contents bibliographic data bases from August 1980 to June 1997. The statistical evaluation considered the prognostic influence of the prevalence of micrometastatic cells in bone marrow on relapse-free and/or overall survival. The comparable effect estimate and its corresponding 95% confidence interval (CI) were calculated with the Mantel-Haenszel method using the originally published data of the retrieved studies. RESULTS The presence of epithelial cells in bone marrow was detectable in all carcinoma types, with a median prevalence of approximately 35%. Fourteen of 20 studies found a positive correlation between positive BMM status and reduced relapse-free survival by univariate analysis, but only five of 11 studies confirmed positive BMM status as an independent predictor of short disease-free survival. Regarding overall survival, positive BMM status was identified univariately in five of 12 studies, but multivariately in only two studies, as an independent factor of poor survival. Despite the heterogeneity of the studies, calculation of the relative risk (RR) for reduced relapse-free survival was possible for breast cancer, which resulted in a Mantel-Haenszel RR (RR(MH)) of 1.34 (95% CI, 1.27 to 1.42). CONCLUSION In conclusion, the results suggest that the prognostic impact of epithelial cells in bone marrow remains to be substantiated by further studies using standardized methodic protocols before its entrance in the TNM classification.

Donor-Recipient Mismatches in MHC Class I Chain-Related Gene a (MICA) in Unrelated Donor (UD) Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 58-58
Author(s):  
Marcos De Lima ◽  
Morgani Rodrigues ◽  
Pedro Cano ◽  
Peter Stastny ◽  
Ping Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Class I ◽  
Unrelated Donor ◽  
Multivariate Models ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade Ii ◽  
The Impact

Abstract MICA is a highly polymorphic locus located in the Class III region of the HLA system in the short arm of chromosome 6. The products of MICA can elicit humoral allo-recognition and are the ligands of the NKG2-D receptors of natural killer cells. MICA is involved in chronic and possibly acute graft rejection in kidney transplantation. The impact of mismatches in MICA has not been examined systematically in bone marrow transplantation. We hypothesized that donor-recipient MICA mismatches may influence graft-versus-host disease (GVHD) and relapse rates after UD hematopoietic stem cell transplantation (HSCT), and tested this hypothesis in a cohort comprised of all patients with myeloid leukemias transplanted in our institution from January, 2002 to December, 2007 (n=238). Methods: Typing of each of the classical human leukocyte antigen (HLA) and MICA loci was performed by amplification with locus-specific primers of genomic DNA by PCR followed by nucleotide sequencing. For the assignment of MICA alleles, the polymorphisms in exons 2, 3, 4, and 5 were evaluated. Matching grade is described in the GVH direction. Outcomes were acute (a) GVHD incidence, and aGVHD-free survival (time dependent variable, with development of aGVHD as the event), and relapse-free survival (RFS), both estimated by the Kaplan Meier method. Cox proportional hazards regression model was used to estimate the influence of HLA match degree, patient, disease, and transplant-related characteristics on outcomes. Median age was 50 years (range, 18–74; 24% over age 59). Diagnosis were AML/high-risk MDS in 82% (n=195) and CML in 18% (n=43). 42% (n=100) of the patients were in remission (CR) at HSCT. Preparative regimens were ablative in 59% (n=141), and contained ATG, fludarabine and IV busulfan in respectively 96%, 90% and 70% of the HSCT. GVHD prophylaxis was tacrolimus and mini-methotrexate-based in all HSCT. Stem cell source was bone marrow (BM) in 72% (n=172) and peripheral blood (PB) in 28% (n=66) of HSCT. 78 patients have relapsed (34%) and 133 have died (56%). Results. 169 pairs were matched in HLA A, B, C, DRB1, and DQB1 (10/10; 71%); 69 (29%) were <10/10 matches, of which 60 were 9/10 (78% of the mismatches were in HLA class I). One or two HLA-DPB1 mismatches were present in 48% and 25% of the patients, respectively. MICA one or two mismatches were present in 22 pairs (9%). Grade (gd) II–IV and III–IV aGVHD rates for patients with MICA mismatches were 80% and 30%, respectively, versus 40% and 14% for those with no MICA mismatches. Effect of MICA on aGVHD was similar among 10/10 and <10/10 patients. RFS at 52 weeks post HSCT was 0.58 (95%CI 0.5–0.66) versus 0.77 (95%CI 0.59–1) for patients without and with MICA mismatches (P=0.5). Multivariate models are shown in the table. Conclusion: MICA mismatches independently increased the incidence of grade II–IV aGVHD. Multivariate Models for grade II-IV acute GVHD and relapse-free survival (RFS) Variable Incidence Univariate P value Multivariate P, HR and 95% CI Grade II-IV aGVHD Fludarabine-based regimen(yes vs no) 39% vs 72% P=0.0009 0.02; HR 0.51 (0.29–0.9) DPB1 mismatches (0/1 vs 2) 38% vs 52% P=0.06 0.03; HR 0.59 (0.37–0.94) Ablative conditioning (no vs yes) 31% vs 48% P=0.001 0.05; HR 0.65 (0.43–0.99) MICA mismatches (yes vs no) 80% vs 38% P=0.0002 0.002; HR 2.33 (1.37–3.98) RFS Rate at 52 weeks 95%CI Univariate P Multivariate P, HR and 95% CI DPB1 (0 vs 1 vs 2) 0.54(0.42, 0.68) P=0.09 0.03; HR 1.65 (1.051–2.6) 0.55(0.45, 0.67) 0.7(0.58, 0.84) CR at HSCT (yes vs no) 0.78(0.69, 0.87) P<0.0001 <0.0001; HR 0.308 (0.18–0.52) 0.44(0.36, 0.55) (P and HR for aGVHD-free survival) HR: hazard ratio; CI: confidence interval

scholarly journals Successful therapy of convoluted T-lymphoblastic lymphoma in the adult

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 92-98 ◽  
Author(s):  
AM Levine ◽  
SJ Forman ◽  
PR Meyer ◽  
SC Koehler ◽  
H Liebman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Bone Marrow Involvement ◽  
Cranial Irradiation ◽  
Lymphoblastic Lymphoma ◽  
Intrathecal Methotrexate ◽  
Induction Phase ◽  
Relapse Free Survival ◽  
Free Survival ◽  
T Lymphoblastic Lymphoma

Abstract Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16–73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

Long-Term Outcomes in Patients with Acute Myelogenous Leukemia (AML) Following Allogeneic Stem Cell Transplantation (AlloSCT) for Relapse After Initial Autologous Bone Marrow Transplant (ASCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2299-2299
Author(s):  
Mary-Elizabeth Percival ◽  
Lloyd E. Damon ◽  
Thomas Martin ◽  
Lawrence Kaplan ◽  
Weiyun Ai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Response Status

Abstract Abstract 2299 Poster Board II-276 Introduction: Patients with low- and intermediate-risk AML have several options for consolidation therapy, including chemotherapy alone and ACST or AlloSCT. Since randomized studies comparing these approaches show no option to be clearly superior to the others, several centers focus on sequencing of therapies in terms of patient tolerance and toxicity. Since 1986 our preferred consolidation regimen at UCSF for these patients consists of high-dose chemotherapy with ASCT. Consequently, at the time of relapse, we are often presented with the need for a second transplant (usually AlloSCT), in the setting of prior ASCT. As there is a paucity of data describing the toxicity and efficacy of AlloSCT in this setting, we designed this study to evaluate these parameters. Patients and Methods: This is a retrospective-cohort, single-institution study of patients with AML treated at UCSF between 1986 and 2008 and who received a second transplant at the time of relapse. Patients were identified through our prospective database, and data were collected from electronic medical records and primary clinical charts when available. Dates of death were corroborated with the social security database. Statistical analysis was performed using STATA (v9). Censoring date for all analyses was July 31st, 2009. This study was approved by the UCSF institutional review board. Results: Thirty-one patients with AML were identified who underwent an AlloSCT in the setting of relapse following a prior ASCT, with a median follow up of 54 months. The median time from the first to the second transplant was 17 months (range: 6 – 48). The median age at the time of the AlloSCT was 43 years (range: 20 – 64). Response status at the time of transplant was: 17 patients (55%) in complete remission (CR), 12 patients (39%) with less than CR, and 2 patients (6%) with response status unknown. The transplant was myeloablative in 14 patients (45%), non-myeloablative in 13 patients (42%), and cord-blood-based in 4 patients (13%). The donor was unrelated in 17 patients (55%). There were 7 (18%) treatment-related deaths in the first 6 months and 10 (32%) treatment-related deaths overall (pulmonary toxicity: 4, graft-versus-host-disease: 3, and infection: 3). Twelve patients (39%) died due to progressive disease. The median overall survival was 7 months, with 48% and 31% of patients being alive at 12 and 24 months respectively. Remission status prior to transplant was the most significant predictor of survival; the median survival among complete responders vs. all others was 19 months vs. 3.5 months respectively (p=0.006). Following transplantation, the median relapse-free survival among responders was 38 months, with 31% of patients being relapse-free at last follow-up. The time between transplants, as well as age, sex, and intensity of conditioning regimen had no effect on overall and relapse-free survival in our cohort. However, peripheral stem cell transplant was associated with improved overall survival (compared to bone marrow, p=0.02), though this likely reflects different eras of supportive therapy. Conclusions: Our results suggest that AlloSCT is an effective approach for patients with AML with relapsed or refractory disease after a prior ASCT. In this cohort spanning 22 years, treatment-related mortality from AlloSCT was 32%, and 31% of responders remain free of relapse with long-term follow-up. Disclosures: No relevant conflicts of interest to declare.

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