Cytogenetic Classification Systems and Overall Survival Following Bone Marrow Transplant (BMT) for Acute Myelogenous Leukemia (AML).

Abstract Risk-adapted therapy for AML in first complete remission generally calls for allogeneic BMT for patients with poor risk cytogenetics. However, poor risk cytogenetics is defined differently in commonly-applied classification schemes. We hypothesized that differences in cytogenetic classification might result in differences in survival after BMT. From September 1991 to December 2003, we treated 47 patients with AML in first complete remission with high-dose busulfan-containing preparative regimens and an HLA-matched sibling BMT. The median age was 42 years (range 18 to 60). At the time of diagnosis, 35 patients had either a normal karyotype or at least one clonal abnormality. Cytogenetic analysis was unavailable for the other 12 patients. The 47 patients were then classified according to the SWOG/ECOG (Blood96:4075, 2000), MRC (Blood92:2322, 1998), or CALGB (Blood100:4325, 2002) cytogenetic classification systems and analyzed for overall survival. With a median follow-up of 4.9 years, 3 year overall survival for various cytogenetic risk groups are displayed in the table: SWOG/ECOG CALGB MRC Intermediate risk 69% 63% 74% Poor risk 43% 42% 18% Unknown risk 45% 52% 45% Concordance indices were 0.58 for CALGB, 0.60 for SWOG, and 0.66 for MRC, demonstrating a slight superiority of the MRC system. Consistent with reports of large, prospective randomized trials of BMT for AML in first remission, patients with poor risk cytogenetics have worse overall survival compared to patients with intermediate risk cytogenetics. Overall survival appears to be different for patients classified as poor risk by MRC criteria. Larger, prospective studies are needed to confirm this observation, but our results suggest that standardized, international cytogenetic risk criteria are needed to develop risk-adapted strategies for the treatment of AML.

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Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Blood ◽

10.1182/blood.v82.9.2920.2920 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2920-2928 ◽

Cited By ~ 78

Author(s):

DS Snyder ◽

NJ Chao ◽

MD Amylon ◽

J Taguchi ◽

GD Long ◽

...

Keyword(s):

Bone Marrow ◽

Complete Remission ◽

Acute Leukemia ◽

Lymphoblastic Leukemia ◽

Myelogenous Leukemia ◽

High Dose ◽

Graft Versus Host ◽

Acute Myelogenous ◽

Total Body ◽

First Complete Remission

Abstract Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

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Prognostic Impact of Different High Risk Features in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in First Complete Remission.

Blood ◽

10.1182/blood.v114.22.2303.2303 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2303-2303

Author(s):

Theis Terwey ◽

Philipp Hemmati ◽

Gero Massenkeil ◽

Bernd Dörken ◽

Renate Arnold

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Complete Remission ◽

Lymphoblastic Leukemia ◽

High Dose ◽

Prognostic Impact ◽

Very High ◽

First Complete Remission

Abstract Abstract 2303 Poster Board II-280 Introduction: In acute lymphoblastic leukemia (ALL) specific clinical and biological features confer high relapse risk and inferior overall survival (OS) after treatment with conventional chemotherapy alone. The differential prognostic impact of these high risk features after treatment with allogeneic hematopoietic stem cell transplantation (HCT) has not been well studied. Patients and Methods: 79 adult ALL patients in first complete remission (CR) received allogeneic HCT at our center between 1995 and 2008. All patients were high or very high risk according to German Multicenter Study Group for Adult ALL (GMALL) criteria. Median age was 36 years (range: 17-68). Patients received high-dose conditioning consisting of 12 Gy total body irradiation ± etoposide ± cyclophosphamide (n=69, 87%) or reduced intensity conditioning (RIC) consisting of fludarabine/busulfan/ATG (n=10, 13%) and HSCT from related (n=34, 43%) or unrelated (n=45, 57%) donors. Bone marrow (n=17, 22%) or peripheral blood stem cells (n=62, 78%) were given. Graft-versus-host-disease prophylaxis was CSA/MTX for high-dose conditioning or CSA/MMF for RIC. Results: Patients were classified as high risk or very high risk due to Philadelphia chromosome-positive disease (Ph+) (n=30, 38%), leukocytosis>30/nl at diagnosis in B-ALL (n=25, 23%), late response to induction therapy in B-ALL (>week 4) (n=13, 16%), early or mature T-ALL (n=13, 16%), pro-B-ALL/t(4;11) (n=8, 10%), persistence of minimal residual disease (MRD) (>week 16) (n=8, 10%) or complex aberrant karyotype (n=6, 8%). 57 patients (72%) presented with one high risk feature, whereas 20 patients (25%) and 2 patients (3%) presented with two or three features, respectively. Currently, after a median follow-up of 56 months (7-169) 49 patients (62%) remain alive. Projected OS of the whole cohort at 1, 2 and 5 years was 78%, 70% and 55% and leukemia-free survival was 77%, 66% and 55%. Cumulative incidence of non-relapse mortality (NRM) and relapse mortality (RM) at 5 years was 23% and 18%, respectively. In multivariate Cox regression analysis, a non-significant trend for inferior OS was seen for patients with early or mature T-ALL (hazard ratio (HR): 2.03 (95%CI: 0.92-4.52), p=0.082), whereas no differential effect on OS, NRM or RM was seen for any other high risk feature (Table 1). In additional analyses, inferior OS (HR 1.81 (95%CI: 1.02-3.29), p=0.043) and increased RM (HR 2.17 (95%CI 1.16-4.05), p=0.015) was observed for patients with more than one high risk feature. Conclusions: In summary, this single center study on allogeneic HCT in high risk ALL found a negative prognostic trend for early or mature T cell immunophenotype. No differential prognostic impact on OS, NRM and RM was seen for other high risk features as defined by GMALL criteria, however this conclusion is limited by the low patient number in some of the subgroups. Overall survival for the whole cohort was 55% at 5 years, with inferior OS and higher RM being observed in patients with more than one high risk feature. Disclosures: No relevant conflicts of interest to declare.

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High-dose cytarabine-based consolidation shows superior results for older AML patients with intermediate risk cytogenetics in first complete remission

Leukemia Research ◽

10.1016/j.leukres.2013.01.001 ◽

2013 ◽

Vol 37 (5) ◽

pp. 556-560 ◽

Cited By ~ 5

Author(s):

Mona Hassanein ◽

Eshetu G. Atenafu ◽

Andre C. Schuh ◽

Karen W.L. Yee ◽

Mark D. Minden ◽

...

Keyword(s):

Complete Remission ◽

High Dose ◽

Intermediate Risk ◽

High Dose Cytarabine ◽

First Complete Remission

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Rituximab Plus Hypercvad (R-HCVAD) Alternating with Rituximab Plus High-Dose Methotrexate-Cytarabine (R-M/A) in Untreated Mantle Cell Lymphoma (MCL): Prolonged Follow-Up Confirms High Rates of Failure-Free Survival (FFS) and Overall Survival (OS).

Blood ◽

10.1182/blood.v104.11.128.128 ◽

2004 ◽

Vol 104 (11) ◽

pp. 128-128 ◽

Cited By ~ 5

Author(s):

Jorge Enrique Romaguera ◽

Luis Fayad ◽

Maria A. Rodriguez ◽

Fredrick B. Hagemeister ◽

Barbara Pro ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Complete Remission ◽

Stem Cell Transplant ◽

Pulmonary Hemorrhage ◽

Myelogenous Leukemia ◽

High Dose ◽

Hematologic Toxicity ◽

Cell Transplant

Abstract Introduction: Aggressive MCL has a poor prognosis with a 21-40% complete remission (CR) after CHOP and a duration of response of only 10-16 months. More intense therapy could improve these statistics. Rituximab is effective in MCL and has minimal toxicity. Methods: A prospective phase II trial of R-HCVAD (considered to be one cycle) alternating every 21 days with R- M/A (considered to be another cycle) as described earlier (Ann Oncol. 13, suppl 2, 2002 #24). Prophylaxis with mesna, calcium leucovorin, prednisone eyedrops, G-CSF, antibacterial, antifungal, and antiviral therapy. CBC with differential and platelet counts X 2-3/week. Re-staging every 2 cycles including upper and lower endoscopies. Patients in complete remission (CR) after 6 courses of a planned 6-8 cycles were not offered consolidation with stem cell transplant. Post-treatment evaluation was performed every 3 months for 1 yr, every 4 months for 2 yrs, every 6 months for 2 years, then annually. Results: Of 100 patients registered, one was ineligible and two decided to not receive the treatment after registration, leaving 97 evaluable for analysis of response, survival and toxicity. An analysis of response after the first 6 cycles shows an 87% CR/CRu rate. With a median follow up of 40 months, the 3-year FFS and overall survival (OS) were 67% and 81%, respectively. Adverse factors for FFS were: Grade 4 hematologic toxicity was significant. Five patients died during treatment of sepsis (3), pulmonary hemorrhage (1), and unknown cause (1). Four patients developed myelodysplasia/acute myelogenous leukemia after treatment and while in CR and three have died, for a total of 8 deaths in the study (8%). Conclusion: R-HCVAD alternating with R-M/A without stem cell transplant is an effective regimen for treatment of aggressive untreated MCL, specially for patients ≤ 65 years old. Toxicity is as expected for an intense regimen. This encouraging data warrants continued follow-up and comparison with existing/new therapies in future trials.

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Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission

Blood ◽

10.1182/blood.v82.9.2920.bloodjournal8292920 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2920-2928 ◽

Cited By ~ 1

Author(s):

DS Snyder ◽

NJ Chao ◽

MD Amylon ◽

J Taguchi ◽

GD Long ◽

...

Keyword(s):

Bone Marrow ◽

Complete Remission ◽

Acute Leukemia ◽

Lymphoblastic Leukemia ◽

Myelogenous Leukemia ◽

High Dose ◽

Graft Versus Host ◽

Acute Myelogenous ◽

Total Body ◽

First Complete Remission

Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

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Risk Classification for Overall Survival by the Neutrophil–Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab—A Multicenter Collaborative Study in Japan

Cancers ◽

10.3390/cancers13143554 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3554

Author(s):

Taizo Uchimoto ◽

Kazumasa Komura ◽

Wataru Fukuokaya ◽

Takahiro Kimura ◽

Kazuhiro Takahashi ◽

...

Keyword(s):

Overall Survival ◽

Risk Model ◽

Risk Group ◽

Objective Response ◽

Collaborative Study ◽

Risk Groups ◽

Intermediate Risk ◽

Neutrophil Lymphocyte Ratio ◽

Poor Risk ◽

Metastatic Sites

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

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CGE19-065: Number of Somatic Mutations Is an Independent Predictor of Overall Survival in Acute Myeloid Leukemia

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7116 ◽

2019 ◽

Vol 17 (3.5) ◽

pp. CGE19-065

Author(s):

Zin W. Myint ◽

Rani Jayswal ◽

Ranjana Arora ◽

Gregory P. Monohan ◽

Amit Goldberg ◽

...

Keyword(s):

Overall Survival ◽

Myeloid Leukemia ◽

Somatic Mutations ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Intermediate Risk ◽

Poor Risk ◽

Baseline Characteristics ◽

Clinically Significant

Purpose: Acute myeloid leukemia (AML) is characterized by multiple somatically acquired mutations that affect genes of different functional categories. It has been well established in myelodysplastic syndrome (MDS) that the cumulative number of somatic mutations has an impact on overall survival. However, no such data exist for AML. In this study, we sought to determine the number of clinically significant somatic mutations for each cytogenetically defined risk group of AML and to determine whether this had an impact on overall survival (OS). Methods: In this retrospective, single-center study, all adult patients diagnosed with AML from August 2016–December 2017 were reviewed. Baseline characteristics, somatic mutations in the diagnostic bone marrow as detected by Next Generation Sequencing (NGS), and survival outcomes were analyzed. NGS panel was done in-house and could identify 94 genes. Patients were divided into favorable, intermediate, and poor risk groups based on cytogenetics, and molecular abnormalities using NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML, version 1.2018. Kaplan-Meier plots and Cox regression analyses were utilized. Results: A total of 105 AML patients were included; baseline characteristics and frequency of identified clinically significant (CS) mutations are described in the presentation. The FLT3 mutation occurred in the highest frequency (22%) followed by DNMT3A & ASXL1 (15%). 17 (16%) patients were favorable risk, 33 (31%) intermediate risk, and 55 (52%) were poor risk. 67.6% of patients were male, and the median age was 64 (20–79) years. There was a difference in the number of CS mutations between the intermediate risk group and favorable risk group (P=.007), but not between the favorable risk and poor risk groups (P=.221) or between the intermediate risk group and poor risk group (P=.093). Increased number of CS mutations (≥ 5) was seen with equal frequency across risk groups and predicted for shorter overall survival in both univariate (HR=2.80; P=.039) and by multivariate Cox regression analysis (P=.001) independently from assigned risk group. There were no differences in age, gender, smoke, geographic, and different risk groups by multivariate analyses. Conclusion: Our study shows that ≥ 5clinically significant somatic mutations were associated with adverse outcomes and decreased survival, independent of risk groups and induction regimen. Thus, it may be a useful prognostic factor. This finding needs to be validated using a larger sample size.

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