PR1 Peptide Vaccine-Induced Immune Response Is Associated with Better Event-Free Survival in Patients with Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 283-283 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Eric D. Wieder ◽  
Peter F. Thall ◽  
Xuemei Wang ◽  
Rosa L. Rios ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Peptide Vaccine ◽  
Fold Increase ◽  
Specific Immune Response ◽  
Event Free Survival ◽  
Free Survival ◽  
Measurable Disease

Abstract Background: PR1 is a nonomeric HLA-A2-restricted peptide derived from the myeloid leukemia-associated antigens, proteinase 3 and neutrophil elastase. PR1-specific cytotoxic T lymphocytes (PR1-CTL) selectively kill MDS, AML and CML and contribute to complete cytogenetic remission. We conducted a phase I/randomized phase II trial to evaluate the safety and efficacy of a PR1 peptide vaccine to elicit PR1-CTL in leukemia patients. Methods: Sixty-six HLA-A2+ patients with acute myeloid leukemia (42), chronic myeloid leukemia (13) or myelodysplastic syndrome (11) were treated with PR1 peptide vaccine. The first 54 patient received three vaccinations, and the last 12 patients received 6 vaccinations. PR1 was injected with incomplete Freud’s adjuvant (Montanide ISA) subcutaneously, at 3 week intervals at one of three dose levels: 0.25, 0.5 or 1.0 mg per vaccination. GM-CSF at a dose of 75 mg was injected subcutaneously into the same site. Immune response to the vaccine was defined as a ≥ 2-fold increase in peripheral blood PR1-CTL. Fifty-three patients had measurable disease and 13 were in complete remission at enrollment. Results: The vaccine was well tolerated, with toxicity limited to grade I and II injection site reactions. PR1-specific immune response was observed in 25/53 (47%) patients with measurable disease. Clinical responses were observed in 9/25 (36%) immune responders versus 3/28 (10%) immune non-responders (p=0.03). The PR1 vaccine-induced immune response was associated with a longer event-free survival, 8.7 months vs. 2.4 months (p = 0.03), and a trend towards longer overall survival. Among the 13 patients treated in complete remission, 4 have remained in remission for a median of 30.5 months (range 11–59 months). This includes continued complete remissions in 3/10 who were IRV+, and 1/3 who were IRV-. PR1-specific immune response lasted for up to 4 years in some patients. In a multivariate model, low bone marrow blast count (<10%) emerged as a significant predictor of an immune response and a longer event-free survival (p=0.001). Conclusion: PR1 peptide vaccine-induced immune response is associated with a clinical response and better event-free survival in patients with myeloid leukemia, who had measurable disease at vaccination. Patients with ≤10% bone marrow blasts are likely to obtain the maximum benefit. Figure Figure

PR1 peptide vaccination for patients with myeloid leukemias

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7017-7017
Author(s):  
M. H. Qazilbash ◽  
P. F. Thall ◽  
X. Wang ◽  
E. Wieder ◽  
R. Rios ◽  
...  
Keyword(s):  
Immune Response ◽  
Myeloid Leukemia ◽  
Peptide Vaccine ◽  
Fold Increase ◽  
Event Free Survival ◽  
Free Survival ◽  
Injection Site Reactions ◽  
Clinical Responses ◽  
Blast Count ◽  
Dose Levels

7017 Background: PR1 is a nanomeric HLA-A2-restricted peptide derived from the myeloid leukemia-associated antigens proteinase 3 and neutrophil elastase. Methods: Sixty-six HLA-A2+ patients with acute myeloid leukemia (42), chronic myeloid leukemia (13) or myelodysplastic syndrome (11) were treated with PR1 peptide vaccine. The first 54 patient received three vaccinations, and the last 12 patients were given six vaccinations. The vaccine was injected subcutaneously, at 3 week intervals at one of three dose levels: 0.25, 0.5 or 1.0 mg per vaccination. Immune response to the vaccine was defined as a ≥ 2-fold increase in PR1-specific cytotoxic T lymphocytes. Results: Fifty-three patients had measurable disease (MD) and 13 were in complete remission. The vaccine was well tolerated, with toxicity limited to grade I and II injection site reactions. Forty-four of the 53 patients with MD were evaluable for both immune and clinical responses. PR1-specific immune response was observed in 35/44 (57%) of the evaluable patients. Clinical responses were observed in 10 of the 25 immune responders versus 2 of the 19 immune non-responders (p=0.04). PR1 vaccine-induced immune response was associated with a longer event-free survival, 8.7 months vs. 4.1 months in immune non-responders (p = 0.17). Older age and high blast count were associated with short event-free survival (p=0.01 and <0.001). Conclusion: PR1 peptide vaccine-induced immune response is associated with a superior overall clinical response and a trend towards longer event-free survival in patients with persistent myeloid leukemia. [Table: see text]

Childhood acute myeloid leukemia: outcome in a single center using chemotherapy and consolidation with busulfan/cyclophosphamide for bone marrow transplantation.

1994 ◽  
Vol 12 (10) ◽  
pp. 2138-2145 ◽  
Author(s):  
P J Shaw ◽  
M E Bergin ◽  
M A Burgess ◽  
L Dalla Pozza ◽  
S J Kellie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Bone Marrow Transplantation ◽  
Survival Rate ◽  
Complete Remission ◽  
Relapse Rate ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Free Survival ◽  
Acute Myeloid

PURPOSE To report the impact of bone marrow transplantation (BMT) with busulfan/cyclophosphamide (BuCy) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia (AML). PATIENTS AND METHODS Between May 1987 and November 1992, 43 patients were diagnosed with AML. Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy. Conditioning for BMT was with BuCy, followed by allogeneic or unpurged autologous marrow infusion. RESULTS Of 37 patients who received chemotherapy, 35 achieved remission (95%) after one to six courses of treatment and 34 (92%) were transplanted. Five relapsed before BMT, four were subsequently transplanted in second complete remission (CR2) (n = 3) or untreated first relapse (n = 1), and one failed to respond to further therapy. All other patients proceeded to BMT in first complete remission (CR1). Eleven patients received allografts: one relapsed and one died of graft-versus-host disease (GvHD), for a leukemia-free survival rate of 90% at a median of 41 months after BMT (range, 3 to 60). For 23 autografts, there were two toxic deaths and eight relapses, with a leukemia-free survival rate of 61% at a median of 11 months after BMT (range, 0 to 66). The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu. CONCLUSION With modern supportive therapy, most newly diagnosed children with AML will enter remission and are eligible for intensification therapy. BuCy is well tolerated in children, which allowed us to escalate the dose of Bu in recent patients. Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT.

scholarly journals High Expression of Myocyte Enhancer Factor 2C (MEF2C) Is Associated with Adverse Risk Features and Poor Outcome in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2570-2570
Author(s):  
George S. Laszlo ◽  
Todd A. Alonzo ◽  
Chelsea J. Gudgeon ◽  
Kimberly H. Harrington ◽  
Alex Kentsis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Event Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Acute Myeloid ◽  
Enhancer Factor

Abstract Background: Myocyte enhancer factor 2C (MEF2C) was initially identified as essential transcription factor for cardiac muscle development. However, subsequent studies have indicated that MEF2C plays a much broader biological role, including in the normal hematopoietic system. Recent studies have now identified MEF2C as cooperating oncogene in acute myeloid leukemia (AML) and suggested a contribution to the aggressive nature of at least some subtypes of AML. These findings raised the possibility that MEF2C could serve as marker of poor-risk disease and, therefore, have prognostic significance in AML. To test this hypothesis, we retrospectively quantified MEF2C expression in participants of the AAML0531 trial and correlated expression levels with disease characteristics and clinical outcome. Patients and Methods: AAML0531 (NCT00372593) was a multicenter phase 3 study that determined the addition of gemtuzumab ozogamicin to intensive chemotherapy among 1,022 eligible patients aged <30 yearswith newly diagnosed de novo non-APL AML, excluding those with bone marrow failure syndromes, juvenile myelomonocytic leukemia, or Down syndrome (if ≤3 years of age) between 2006 and 2010. Cryopreserved pretreatment ("diagnostic") specimens from patients enrolled on AAML0531 who consented to the biology studies and had bone marrow samples were available were included in this study. Total RNA from unsorted specimens was extracted, quantified, and subjected to quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) using TaqMan primers to determine expression of MEF2C and, for normalization, the housekeeping gene, β-glucuronidase (GUSB). Patient samples were run in duplicate, and the ΔΔCT method quantified as 2(-ΔΔCT) was used to determine the expression levels of MEF2C relative to GUSB. Results: In all 751 available patient specimens, MEF2C mRNA was detectable and varied >3,000-fold relative to GUSB (0.0091-29.1272 [median: 0.7978]). Patients with the highest relative MEF2C expression (4th quartile) less likely achieved a complete remission after one course of chemotherapy than the other patients (67% vs. 78%, P=0.005). They also had an inferior overall survival (P=0.014; at 5 years: 55±8% vs. 67±4%), inferior event-free survival (P<0.001; at 5 years: 38±7% vs. 54±4%), and higher relapse risk than patients within the lower 3 quartiles of MEF2C expression (P<0.001; at 5 years: 53±9% vs. 35±5%). Of note, exploratory multiple cutpoint analyses for overall and event-free survival indicated that the most statistically significant results were centered around the Q4 cutpoint region, supporting our approach of comparing patients with the highest quartile of relative MEF2C expression with those having lower relative MEF2C expression. Importantly, MEF2C expression was strongly associated with cytogenetic and molecular abnormalities. Specifically, patients with high MEF2C expression less likely had CBF translocations (inv(16): P=0.007, and t(8;21): P<0.001) or normal karyotype AML (P<0.001); conversely, they were more likely to have leukemia with monosomy 7 (P<0.001) and abnormalities involving 11q23 (P<0.001). Furthermore, patients with high MEF2C less likely had a FLT3/ITD (P =0.018) or a mutation in either NPM1 (P=0.010) or CEBPA (P =0.002). Consistently, patients with high MEF2C expression less likely had low-risk disease (16% vs. 46%, P<0.001) and more likely had standard-risk disease (68% vs. 42%, P <0.001) than those with lower MEF2C expression. Indeed, after adjustment for disease risk, age, FAB category, and treatment arm, high MEF2C expression was no longer statistically significantly associated with inferior overall survival (hazard ratio [HR]=0.99 [95% confidence interval: 0.72-1.36], P=0.929), inferior event-free survival (HR: 1.14 [0.86-1.49], P=0.365), or higher relapse risk (HR: 1.32 [0.91-1.92], P=0.137), suggesting that MEF2C cooperates with additional pathogenic abnormalities. Conclusion: High MEF2C expression identifies a subset of AML patients with adverse-risk disease features and poor outcome. These findings provide the rationale for therapeutic targeting of MEF2C transcriptional activation in AML. Disclosures Walter: AstraZeneca, Inc.: Consultancy; Covagen AG: Consultancy; Seattle Genetics, Inc.: Research Funding; Amgen, Inc.: Research Funding; Pfizer, Inc.: Consultancy; Amphivena Therapeutics, Inc.: Consultancy, Research Funding.

The Addition of Rituximab to High Dose Sequential Chemotherapy (HDS) Programs with Autologous Transplantation Significantly Improves the Outcome of Patients with Refractory or Relapsed B-Cell Non Hogkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2084-2084
Author(s):  
Sergio Cortelazzo ◽  
Andrea Rossi ◽  
Emanuela Carlotti ◽  
Piera Viero ◽  
Alessandro Rambaldi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Complete Remission ◽  
Peripheral Blood ◽  
Response Rate ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Event Free Survival ◽  
Free Survival

Abstract The aim of the present study was to evaluate retrospectively the clinical outcome of 2 consecutive cohorts of relapsed/refractory NHL patients treated with HDS chemotherapy with and without Rituximab and autologous peripheral blood stem cell (PBSC) transplantation. A total of 110 relapsed or refractory NHL patients with different histology (SLL n= 4, FL n=24, Low grade-transformed n=31, DLBCL n=51) entered this analysis. From October 1992 up to November 2004, patients were treated with the original HDS program (n= 33, HDS: cyclophosphamide 7 gr/sqm, methotrexate 8 gr/sqm, etoposide 2 gr/sqm) (Gianni AM et al.: N.Engl.J.Med., 1997) or a modified version (n= 15) in which methotrexate was replaced by HD-Ara-C (2 g/sqm every 12 hours for 6 days). Because the addition of Rituximab could improve the antitumor activity and the response rate before transplantation, from June 1999, Rituximab (375 mg /sqm) was given twice after HD-CTX and twice after HD-Ara-C. Following the HDS chemotherapy program, a BEAM (carmustine BCNU, 300 mg/sqm; etoposide, 200 mg/sqm; Ara-C, 4000 mg/sqm; L-PAM 140 mg/sqm) conditioning regimen with autologous PBSC transplantation was planned. By quantitative PCR analysis of BCL2/IgH chimeric gene, a molecular evaluation of minimal residual disease was performed before transplantation and during follow up on bone marrow or peripheral blood obtained from 21 patients. At enrollment, 69 patients (63%) were high risk being primary refractory (39), early relapsed (7) after first line treatment or relapsed more than twice (23). Moreover, an IPI >1 was documented in 62 patients (56%) and a bone marrow infiltration in 42 (38%). Sixteen patients (15%) had received 2 or 3 lines of conventional chemotherapy and 29 (26%) involved field Radiotherapy. At the end of HDS chemotherapy, before the conditioning regimen, the Response Rate was 82% with 76 patients achieving complete remission (CR, 69%) and 14 patients partial remission (PR, 13%). After autologous transplantation, 76 patients remained in CR (69%), 5 in PR (5%), 25 (23%) showed no response or progressive disease. Four patients (3%) died during treatment. Ninety-four patients (85%) could complete the planned program and underwent autologous transplantation and a median number of 6.3 x 10^6 cells CD34+/Kg was transplanted. After transplantation, 24 patients relapsed, 1 patient developed secondary MDS and 1 patient died because of a secondary GI tract solid tumor. With a median follow-up of 28 months (range 3–146), the 5-year estimate overall survival (OS) and event-free survival (EFS) of the whole group of patients is 48% and 39%, respectively. However, the EFS of patients not receiving Rituximab was 27% as compared to 55% registered in the R-HDS program (p= 0.005). The Cox multivariate analysis confirmed an improved OS (p=0.0000) and EFS (0.001) for patients treated with R-HDS. The achievement of a durable molecular remission was achieved in 11 out of 21 analyzed and was strongly associated with the R-HDS program. In conclusion: the response rate of relapsed or refractory NHL after HDS chemotherapy is high and more than 70% of patients can undergo conditioning regimen and autologous transplantation being in complete remission. The addition of Rituximab to HDS chemotherapy allows the collection of tumor free PBSC in most patients and significantly correlates with an improved Event Free Survival and Overall Survival.

Clinical Relevance of IDH1 and IDH2 Mutations and Single Nucleotide Polymorphism (SNP) rs11554137 in Patients with Acute Myeloid Leukemia Treated with Stem Cell Transplant in First Complete Remission

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4643-4643
Author(s):  
Hala Abalkhail ◽  
Naeem A. Chaudhri ◽  
Claudia Ulrike Walter ◽  
Hazzaa Al Zahrani ◽  
Randa Nounou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Snp Polymorphism ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 4643 Background: Mutations in the genes encoding for the cytosolic isocitrate dehydrogenase 1 (IDH1) and the mitochondrial version of this enzyme (IDH2) have been reported in acute myeloid leukemia (AML) and other types of cancer. Presence of these mutations in AML correlated with more aggressive disease in some studies, but other studies did not find significant correlation with outcome when patients were treated with intensive chemotherapy. The polymorphism at rs11554137 in IDH1 was reported to correlate with inferior outcome in cytogenetically normal AML patients. Most of the studies evaluating the prognostic relevance of IDH1, IDH2 and the rs11554137 polymorphism were reported in patients treated with standard chemotherapy. The prognostic significance of these markers is not fully studied when AML patients are treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the prognostic value of the IDH1, IDH2, and rs11554137 polymorphism in patients with AML treated with HSCT in first complete remission (CR1). Methods: Samples from 69 patients with AML were analyzed for mutations in IDH1, IDH2, and the SNP rs11554137 by direct sequencing. All patients were diagnosed with AML, treated with chemotherapy followed by HSCT in CR1. They included intermediate (N=42) and adverse (N=27) cytogenetic risk groups. Results: The R132H and the SNP C to T change at rs11554137 (silent G105) in IDH1 were detected in 5 (7%) and 6 (9%) of 69 AML patients. The IDH2 mutations (N=5; 7%) included R140Q, 172K, and T169A. Patients with IDH1 or IDH2 mutations did not differ significantly in their overall survival, event free survival, or time to relapse from those without mutation. In addition, the rs11554137 SNP polymorphism did not correlate with outcome in this group of AML patients. We also looked at the combination of mutations as compared with cytogenetic risk and found no difference in survival or event free survival based on IDH1 or IDH2 mutations or rs11554137 polymorphism in the intermediate cytogenetic risk group. Conclusion: The data suggests that HSCT after intensive chemotherapy in CR1 may neutralize the negative prognostic impact of IDH1 and IDH2 or the rs11554137 SNP polymorphism. However, the number of cases is relatively small and further studies with larger number of cases are needed. Disclosures: No relevant conflicts of interest to declare.

Comparison of idarubicin + ara-C–, fludarabine + ara-C–, and topotecan + ara-C–based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3575-3583 ◽  
Author(s):  
Elihu H. Estey ◽  
Peter F. Thall ◽  
Jorge E. Cortes ◽  
Francis J. Giles ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Confidence Interval ◽  
Myeloid Leukemia ◽  
Refractory Anemia ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
New Treatments ◽  
Acute Myeloid

Abstract It has been unclear whether regimens containing topotecan + ara-C (TA) or fludarabine + ara-C (FA) ± idarubicin are superior to regimens containing idarubicin + ara-C (IA) without either fludarabine or topotecan for treatment of newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or RAEB. Of 1279 patients treated here for these diagnoses between 1991 and 1999, 322 received IA regimens, 600 FA regimens, and 357 TA regimens. All regimens used ara-C doses of 1 to 2 gm/m2/d, given by continuous infusion in IA, and over 2 to 4 hours in FA and TA. Complete remission (CR) rates were lower with FA (55%) and TA (59%) than with IA (77%). Both event-free survival (EFS) in CR and survival were shorter: median EFS in CR (95% confidence interval) was 63 weeks (range, 55-76 weeks) for IA, 40 (range, 31-46 weeks) for FA, and 36 (range, 27-44 weeks) for TA; median survival was 77 weeks (range, 57-88 weeks) for IA, 30 (range, 27-35 weeks) for FA, and 41 (range, 35-50 weeks) for TA. These trials were not randomized, and patients with worse prognoses were disproportionately given the FA and TA regimens. Nonetheless, after accounting for prognosis the FA and TA regimens remained highly significantly associated with lower CR rates, shorter EFS in CR, and shorter survival. Accounting for possible effects of individual trials within each of the IA, FA, and TA groups did not alter these findings. It is unlikely that, as given here, either FA or TA is, in general, superior to IA, highlighting the need for new treatments.

Granulocytic Sarcoma (GS) Is Associated with Event-Free Survival Superior to That of Acute Myeloid Leukemia (AML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2008-2008
Author(s):  
Apostolia-Maria Tsimberidou ◽  
Michael J. Keating ◽  
Hagop M. Kantarjian ◽  
Susan O’Brien ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Posterior Probability ◽  
Granulocytic Sarcoma ◽  
Event Free Survival ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Number Of Patients ◽  
Acute Myeloid

Abstract Introduction. Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature myeloid cells. Some GS patients develop acute myeloid leukemia (AML), but the outcomes of these two diseases have never been compared. The purpose of this retrospective analysis was to compare the rates of response, survival and event-free survival (EFS) of patients treated for GS and patients treated for AML, after adjusting for presenting characteristics. Patients and Methods. We identified 1720 AML and 24 GS patients who presented at The University of Texas M. D. Anderson Cancer Center from 1990 to 2004. All the AML patients and 17 of the GS patients received ara-C + idarubicin or fludarabine. After comparing outcomes in these patients, we accounted for possible differences in underlying prognosis by matching treated GS and AML patients, using cytogenetics, age +/− 3 years, Zubrod performance status (0–2 vs. >2), and time of treatment +/− 3 years as the criteria for matching. Among 9 GS patients age ≤60 years, cytogenetic abnormalities were found at the sarcoma site or in the bone marrow in 5 patients; 4 of these 5 patients had a +8 abnormality, so we matched GS patients ≤60 years with cytogenetics that were “normal” in bone marrow but not assessed in GS tissue with AML patients with a +8 abnormality, assuming the “normal” karyotype in the GS patients was possibly non-informative and thus falsely negative. Among 15 GS patients <60 years old, cytogenetic abnormalities were inv(16) in 2, +8 in 2, 11q del in 1, −7 in 1, and miscellaneous in 2; 7 patients had normal bone marrow cytogenetics but no assessment in GS tissue. On the basis of the frequency of known cytogenetic abnormalities, we matched each of the 7 non-informative GS patients with better-, intermediate-, or worse-risk AML patients. EFS duration was compared in pair-mates of patients, and the Bayesian posterior probability that GS is associated with longer EFS duration was computed. Results. Among treated patients (GS 17, AML 1720), complete response rates were 71% and 57% in GS and AML, respectively (p=0.28). The respective 2-year EFS rates were 82% and 63% (p=0.049), and 2-year overall survival rates were 94% and 77% (p=0.16). Matches could be found for 14 GS patients, who were matched with 91 AML patients (including 3 matched with 2 different GS patients each). The median number of matches was 4 (range, 3–21). EFS duration was longer in 27 AML pairmates, shorter in 55, and unevaluable owing to censoring in 9. Assuming a beta distribution and a priori that 41 matches would have favored GS and 41 AML if EFS was the same in GS and AML, the posterior probability that EFS duration was longer in GS was 0.99. Eliminating the matches involving 1 GS patient and 21 AML patients led to a 0.92 posterior probability of longer EFS duration in GS. Conclusions. Our results suggest that GS is associated with better prognosis than AML based on the superior EFS of GS patients. Differences in rates of CR and survival did not reach statistical significance, possibly because of the small number of patients with GS.

Kinetics of Bone Marrow Blasts during Remission Induction Course in Acute Myeloid Leukemia: Effect on Complete Remission and Relapse-Free Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1852-1852
Author(s):  
Masamitsu Yanada ◽  
Guillermo Garcia-Manero ◽  
Farhad Ravandi ◽  
Stefan Faderl ◽  
Hagop Kantarjian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Persistent Disease ◽  
Bone Marrow Blasts ◽  
Acute Myeloid

Abstract Achievement of complete remission (CR) is crucial to prolong survival in acute myeloid leukemia (AML). The definition of CR has been well established; however, there are no objective measures for deciding when the probability of achieving CR has become so low that a patient’s disease can be considered resistant to therapy. In particular, it can be difficult to distinguish patients with resistant disease from those with persistent disease but who subsequently will enter CR, a distinction that underlies the decision to start a second course or change therapy. We attempted to facilitate this decision by examining the relation between the % marrow blasts 21 days, and later, after start of course 1 of initial induction therapy and the subsequent probability of CR on course 1. Our database consisted of the 593 adults with AML (≥20% blasts, acute promyelocytic leukemia excepted) who had bone marrow examined 21 days after beginning induction therapy including cytarabine at cumulative dose of 5–6 g/m2 at M. D. Anderson Cancer Center from 1995 to 2004. 340 of the 593 patients had an additional bone marrow examination between day 22 and day 28 (day 22–28) of course 1; similarly, day 29–35 marrows were done in 185 patients, day 36–42 marrows in 89 patients and so on. Bone marrows were categorized as morphologic leukemia-free state (MLFS; &lt;5% blasts), persistent disease (PD; ≥5% blasts), or too few cells to count (TFTC). 197 of the 593 patients (33%) had an MLFS on day 21. This conferred a 94% probability of CR on course 1, independent of cytogenetic group. 275 patients (47%) had PD on day 21 and 57% of these 275 entered CR on course 1, with the probability of subsequent CR being predictable from the combination of cytogenetics, day 21 bone marrow blasts, and day 21 platelet and neutrophil counts. Patients with PD on day 21, but who achieved an MLFS on day 28 were highly likely to enter CR (40/47). However, those with PD beyond day 28 were very unlikely to enter CR on course 1, and no CR was observed in patients with PD after day 43. 121 patients (20%) had a TFTC marrow on day 21, with this finding associated with a CR rate of 72% on course 1 (p&lt;0.001 vs MLFS, and p&lt;0.001 vs PD). Not surprisingly given the respective CR rates, patients with MLFS on day 21 had significantly longer survival than patients with PD and patients with TFTC marrow (p&lt;0.001). However, Relapse-free survival was not different among the 3 groups (p=0.109), which was also confirmed by multivariate analysis accounting for cytogenetics, antecedent hematologic disorder, and age. These results appear useful in management of AML, and recommend that bone marrow be examined on day 28, in patients with PD on day 21 and a &lt;50% probability of subsequent CR and in patients with TFTC on day 21. Should PD persist on day 28, and especially on day 35, a second course should be started or new therapy instituted.

Primary Clinical Research of FA Regimen as Consolidation Therapy for Patients with Acute Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4380-4380
Author(s):  
Huina Lu ◽  
Wei Qin ◽  
Aibin Liang
Keyword(s):  
Complete Remission ◽  
Myeloid Leukemia ◽  
Recovery Time ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Event Free Survival ◽  
Free Survival ◽  
Nonhematologic Toxicity ◽  
Wbc Count

Abstract Abstract 4380 In our study, 28 patients with AML treated in our department between 2004 and 2009 under complete remission, median age of 54 years (range 23–77) were consolidated with FA regimen which included fludarabine 30mg/m2 (days 1–3) and Ara-C 2g/m2 (days 1–3). Ara-C were administered as a continuous sequential infusion 4 hours later when the application of fludarabine had been over. Another 14 AML patients with matched conditions treated with high dose Ara-C (HDAra-C, 3g/m2, q12h×3d) were designated as controls. Event-free survival of both 2 groups of these patients were analysed. Overall, 14 patients (50%) achieved continuous complete remission for more than 2 years. There is no statistically significant differences between FA group and HDAra-C group (P=0.214>0.05) in CCR. Patients aged >60 years also had no statistically significant differences compared to the patients aged <60 years in CCR. Seven patients relapsed after this treatment in a median survival of 11 months. Two of the relapsed patients had karyotype abnormalities and all of them had a markedly elevated WBC count at diagnosis. The main toxicity was myelosuppression. WBC count and platelet count reached the lowest (about 0.8×10^9/L and 2.0×10^9/L) 6–13 days after the begining of the regimen. Median recovery time for granulocyte (≥1.0×10^9/L) and platelet (≥20×10^9/L) was 12 and 13 days, respectively. Fever(>38°C) caused by granulopenia occurred in 21 patients, recovered to normal for a median time of 5 days (range, 2–23). Heart, liver and enteric toxicity were negligible. There were no significant differences in hematologic toxicity or nonhematologic toxicity between the FA and HDAra-C group. The average hospitalization was about 20 days. The FA is effective and safe as consolidation regimen in AML with acceptable toxicity and is not associated with an increased incidence of infections compared to conventional HDAra-C regimen. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Treatment of Childhood Acute Myeloid Leukemia in Bulgaria

Folia Medica ◽  
2018 ◽  
Vol 60 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Hasan A. Burnusuzov ◽  
Maya N. Yordanova ◽  
Boryana E. Avramova ◽  
Nadezhda N. Yurukova ◽  
Konstantin N. Bachvarov ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Treatment Protocol ◽  
Event Free Survival ◽  
Treatment Results ◽  
Free Survival ◽  
The Past ◽  
Childhood Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Background: During the last four decades the prognosis of childhood acute myeloid leukemia (AML) has been substantially improved due to an increase in complete remission (CR) rates, event-free survival (EFS) and reduced early mortality. The relapsed AML still remains a therapeutic challenge. Aim: To report the AML treatment results of the Bulgarian pediatric oncohematological centers. Materials and methods: Retrospective analysis of the treatment results of children and adolescents (age from 0 to 20 years) with primary AML. Unified AML BFM- backbone type treatment protocol is used. Results: This study included 97 newly diagnosed patients (44 girls and 53 boys) with AML in Bulgaria between 2003 and 2016. The median age at diagnosis was 10.2 years. The most frequent FAB-morphologic subtype was M2 followed by M4. First complete remission (CR1) was achieved in 83 patients (85.6%). The 13-year EFS was 49%, while the overall survival (OS) was 54.6%. Twenty seven (27.8%) patients relapsed, with only 5 of them being still alive towards the end of the study period. Conclusion: The EFS and OS for the children with AML in Bulgaria are comparable with those reported by other European groups. The prognosis of relapsed AML remains still unfavorable for the past 13 years.

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