The Impact Of European Leukemia Net (ELN) Genetic Classification On The Outcome Of Allogeneic Stem Cell Transplantation (ALLOHCT) For Acute Myeloid Leukemia (AML) In First Complete Remission

Abstract Introduction The improvements in genetic characterization of AML allowed the ELN to propose a prognostic classification into 4 categories: Favorable, Intermediate I, Intermediate II and Adverse. Several groups have tested the outcome of AML patients based on these genetic subgroups in registries and databases from prospective trials. Since ALLOSCT recommendations are being established based on the ELN risk categories, we considered of interest to investigate whether these also have an impact on the results of allogeneic transplants. This could be helpful to identify the patients that may benefit the most from ALLOHCT in the first complete remission (CR1). Objectives To investigate whether the ELN genetic groups of AML have any impact on the results of ALLOHCT performed in CR1. To identify the patients who are best candidates for transplantation, based on the ELN categories as well as in other characteristics. Methods Patients were transplanted between 1990 and 2012. In all cases, treatment prior to transplant had consisted of anthracycline based induction and intermediate-dose cytarabine consolidation according to the CETLAM AML-88, AML-94, AML-99 and AML-03 trials. Upper age limit for transplantation was 60 years until 2002 and 70 years thereafter. Most patients above 50 years received either CD34 selected grafts or reduced intensity conditioning. GVHD prophylaxis after transplant was usually based on cyclosporine and prednisone or methotrexate. The main characteristics of patients and transplants were included in the exploratory analysis of variables influencing survival; those with a p- value up to 0.1 were incorporated as covariates to the multivariable model. Results One hundred ninety two patients in CR1 received an ALLOHCT from HLA-identical siblings (n=140), adult unrelated donors (n=26) or umbilical cord blood (n= 26). Age distribution of the patients was as follows: 16-35 years-old (y-o) n=65 (34%), 36-50 y-o n= 55 (29%), 51-60 y-o n= 54 (28%), >60 y-o n=18 (9%). Twenty-three patients (12%) were classified as in the favorable ELN category, 54 (28%) in the intermediate I, 41 (21%) in the intermediate II and 74 (39%) in the adverse. One-hundred fifty-seven patients (82%) had achieved CR1 after a single course of chemotherapy. Conditioning was myeloablative (MA) in 139 (72%) patients and reduced-intensity (RIC) in 53 (28%). In 76 cases of the MA regimens total body irradiation was included. Thirty-eight patients (20%) died due to transplant complications other than relapse and 47 (24%) experienced a leukemia recurrence. Overall survival (OS) and leukemia-free survivals at 8-years were 55±4% and 53±4%, respectively. Multivariate analysis of factors influencing OS included as covariates age at diagnosis of AML, ELN categories, courses to CR1 and conditioning regimen (MA versus RIC), since they had a p-value <0.1 in the univariate comparisons. The variables with independent on OS impact were age (p=0.01), courses to CR (p=001) and ELN classification (p=0.01). OS at 8 years in the favorable, intermediate I, intermediate II and adverse categories were 69±10%, 53±8%, 69±7% and 42±6%, respectively. In patients from the adverse ELN category, independent factors influencing OS in the multivariate analysis of this subgroup were age (16-60 y-o vs>60, p=0.01) and courses to CR (1 vs more, p=0.03). Conclusions The ELN genetic categories have impact on OS of AML patients who receive an ALLOHCT in CR1. The results were very good in the favorable category and, most important, in intermediate II patients. Even patients in the adverse category had a substantial probability of long-term survival. This is remarkable, since the outcome of patients with adverse genetic features when treated with CT only is very poor. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.6.1217 ◽

1994 ◽

Vol 12 (6) ◽

pp. 1217-1222 ◽

Cited By ~ 67

Author(s):

G Michel ◽

E Gluckman ◽

H Esperou-Bourdeau ◽

J Reiffers ◽

J L Pico ◽

...

Keyword(s):

Bone Marrow ◽

Multivariate Analysis ◽

Bone Marrow Transplantation ◽

High Risk ◽

Complete Remission ◽

Total Body Irradiation ◽

Conditioning Regimen ◽

Total Body ◽

First Complete Remission ◽

Risk Of Relapse

PURPOSE To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

Download Full-text

Autologous Stem Cell Transplantation (ASCT) with Busulfan Plus Cyclophosfamide as Conditioning Regimen for Acute Myeloid Leucemia: Retrospective Experience (1991–2007) of Two Bone Marrow Transplant Unit

Blood ◽

10.1182/blood.v112.11.4453.4453 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4453-4453

Author(s):

Giuseppe Irrera ◽

Giuseppe Messina ◽

Massimo Martino ◽

Giuseppe Console ◽

Giuseppe Milone ◽

...

Keyword(s):

Bone Marrow ◽

Complete Remission ◽

Autologous Bone Marrow Transplantation ◽

Conditioning Regimen ◽

Autologous Bone Marrow ◽

Marrow Transplant ◽

The Impact ◽

First Complete Remission ◽

Related Mortality ◽

Acute Myeloid

Abstract We report our results of ASCT in patients with Acute Myeloid Leukemia (AML) during the last 16 years. Between December 1991 and december 2007, 90 patients with AML received an ASCT. The main characteristics were reported on table 1. The median patient age was 46 years (range17 – 67 years). The conditioning regimen employed for all patients was Busulphan + Cyclophosfamide. The Overall Survival (OS) (Figure1) was 53,5% with a median follow up of 91,6 months. The majority of patients (81) was transplanted in first complete remission (1st CR), 8 in 2nd CR and 1 >2nd CR. The OS considering the disease phase at transplant was different: 55,7% vs 16,7%, p < 0,01 (one pts with > second CR was excluded from analysis). If we considering also the age stratified in two groups: 17–45 vs 46–67 years, all patients in second CR, included into II group died. We have calculated OS stratified for age in these groups that was 46,2% versus 59,6%, respectively, without statistical differences. We also analyzed the OS distributed for sex and cell source without statistical difference. We have documented a statistically significant correlation between FAB group and survival (Figure 2). In fact, the patients with FAB M2 and M4 (excluded M3) had a superior OS than those with other FAB (60,7% vs 40%, p < 0.019)). In 32/40 (80%) patients, the relapse has been documented within 24 months from transplant. The analysis for cytogenetic risk has been performed, but considering only 46 patients assessable. The OS cytogenetic risk-related was 87% for 8 patients with Low Risk, 47% for 36 patients with Intermediate Risk, 2 patients with High Risk died within 11 months from transplant (data not shown). We conclude that autologous bone marrow transplantation is an effective treatment in AML with the possibility of long survivorship, particularly in patients with FAB M2 and M4. In our experience, first complete remission of disease at transplant play an important role and correlates with the longest survival. The analysis of cytogenetic risk reflects the impact of karyotype on OS. Transplant Related Mortality (TRM) has been documented in 6/90 patients, all died before the years 2000. Figure 1 Figure 1. Table 1 Number of patientss 90 Sex (M/F) 42/48 Age (range y) (mean ±SD y) 17–67 46,3±11,4 FAB classification: M0 2 (2,2%) M1 16 (17,8%) M2 28 (31,1%) M3 4 (4,4%) M4 28 (31,1%) M5 11(12,3%) M6 Phase of disease: 1 (1,1%) 1st Complete Remission 81 (90%) 2nd Complete remission 8 (8,9%) > 2nd Complete Remission 1 (1,1%) Citogenetic risk (pts evaluable: 46) Low 8 (17,3%) Intermediate 36 (78,2%) High 2 (4,5%) Transplant Related Mortality 6/90 (6,7%)

Download Full-text

Increasing Genetic Complexity Predicts for Inferior Outcomes Following Reduced-Intensity Conditioning Allogeneic Transplant for Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v118.21.3090.3090 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3090-3090 ◽

Cited By ~ 1

Author(s):

Samantha M. Jaglowski ◽

Nyla A. Heerema ◽

Patrick Elder ◽

John C. Byrd ◽

Steven Devine ◽

...

Keyword(s):

Multivariate Analysis ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Prognostic Indicator ◽

Lymphocytic Leukemia ◽

P Value ◽

Allogeneic Transplant ◽

Reduced Intensity Conditioning ◽

Genetic Complexity ◽

Reduced Intensity

Abstract Abstract 3090 Several biologic markers have been identified which predict an unfavorable course in CLL. Reduced-intensity conditioning (RIC) allogeneic transplant may be able to overcome some of these. This retrospective analysis evaluates the effect of cytogenetics, including metaphase cytogenetics, on outcomes with RIC-allogeneic SCT. From 2005–2011, 51 RIC-allogeneic SCTs were performed at The Ohio State University for CLL. There were 38 males (74.5%) and 13 females (25.5%) with a median age of 58 (range 37–73). The median interval between diagnosis and SCT was 48 months (range 9–270). Before SCT, a median 4 lines of chemotherapy were given (range 1–11). One patient was in CR at the time of SCT, 39 were in PR, and 11 had stable or progressive disease; the median CMI was 3 (range 0–7). Fifty-nine percent of patients had del17; 53% had 3 or more abnormalities on metaphase cytogenetics, and 37% had 5 or more abnormalities. The source was PBSC in 48 (94%), BM in 1 (2%) and CB in 2 (4%). Of the PB or BM SCTs, 19 donors (39.6%) were related and 29 (60.4%) were volunteer; 45 (92%) were matched and 4 (8%) had a 1 allele mismatch. There were 21 (41%) pairs with an ABO mismatch and 16 (31.4%) pairs with a gender mismatch. Conditioning was Flu/Bu +/− ATG in 42 patients (82.2%), FluCamTBI in 6 (11.8%), FluCy in 1 (2%), and FluCyTBI-based in 2 receiving CB (4%). Following transplant, 34 (66.6%) developed AGVHD (gr 1–2: 28, gr 3–4: 6) and 27 of 48 evaluable patients (56.3%) developed CGVHD (limited: 7, extensive: 20). With a median follow-up of 17.3 months (range 1–60), the estimated 3-year OS and PFS following transplant were 56.5% and 42.9% respectively. Table 1 lists variables which had a p-value of ≤0.1 on univariate analysis. The presence of del13 and ≥5 karyotype abnormalities remained significant on multivariate analysis for OS while ≥5 karyotype abnormalities and conditioning with an alemtuzumab-containing regimen were significant for PFS (Table 2). The estimated 3 year OS for patients with del13 was 32.2% and 23% for patients with ≥5 karyotype abnormalities, compared with 72.7% and 73.5% for those without, respectively. The estimated 3-year PFS was 21.5% for patients with ≥5 karyotype abnormalities and 0% for patients with an alemtuzumab-containing regimen and 53.9% and 49.3% for those without, respectively.Table.Variables included in multivariate analysis model.Variablelogrank p-valuePFSOSAge ≥550.0072*…Del13 ≥4.7%0.0039*Del17p ≥5.7%0.0019*0.0878Karyotype abnormalities ≥50.0002*0.0138*Karyotype abnormalities ≥30.0186*0.0623Largest node ≥4 cm0.0277*…Marrow involvement ≥50%0.0752…Alemtuzumab conditioning…0.0001*GVHD prophylaxis0.0001*0.0374*HLA mismatch<0.0001*…*statistically significant at p<0.05Table 2.Multivariate analysis of OS, PFS.OSVariableHR95% CIp-valueDel13q<4.7%1≥4.7%3.581.36 to 9.420.01Karyotype<41≥55.161.97 to 13.560.001PFSVariableHR95% CIp-valueConditioningno alemtuzumab1alemtuzumab9.83.28 to 29.290Karyotype<41≥54.351.67 to 11.280.002 Due to small numbers, the alemtuzumab data should be interpreted with caution, but are consistent with previous reports. Increasing genomic complexity is known to predict for diminished chemosensitivity. Accordingly, the presence of 5 or more abnormalities on metaphase cytogenetics was demonstrated to be a poor prognostic indicator for both PFS and OS following SCT. There was substantial, but not universal, overlap among patients with del17, del13, and highly complex karyotype; this interplay merits further consideration. Better understanding of the evolution of genetic complexity will better define how to time transplant to allow for maximum benefit to those patients likely to evolve.Figure 1.OS and PFS by KaryotypeFigure 1. OS and PFS by Karyotype Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Impact of Infusion Rate on the Early Engraftment Following Allogeneic Intra Bone Marrow Infusion of Hematopoietic Stem Cells in a Canine DLA-Identical Reduced Intensity Transplantation Model

Blood ◽

10.1182/blood.v126.23.5406.5406 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5406-5406

Author(s):

Stephanie Schaefer ◽

Juliane Werner ◽

Sandra Lange ◽

Katja Neumann ◽

Christoph Machka ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Infusion Rate ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

Time Points ◽

The Impact ◽

Reduced Intensity

Abstract Introduction: Direct intra bonemarrow (IBM) infusion of hematopoietic stem cells (HSC) is assumed to improve the homing efficiency and to accelerate the early engraftment in comparison to the conventional intravenous application of HSC. Especially for transplantation of low cell numbers i.e. "weak grafts" that is generally associated with delayed engraftment. The direct infusion of HSC in close proximity to the HSC niche by intra bone marrow transplantation (IBMT) might be a promising way. Whether the HSC infusion rate might influence the homing process and therefore the outcome after IBMT is so far unknown. Aims: Herein, we analyzed in a canine DLA-identical littermate model the impact of different graft infusion rates on the hematopoietic recovery as well as on the engraftment kinetics after IBMT following reduced intensity conditioning. Methods: Recipient dogs received IBMT following a 4.5 Gy total body irradiation (TBI). From day (d) -1 until d+35 Cyclosporin A (15mg/kg) was administered orally twice a day as immunosuppression. For IBM transfusion the graft volume was reduced by buffy coat centrifugation and dogs obtained 2x25 ml simultaneously into the humerus and femur. The infusion rate of the graft was 25ml/10 min in group 1 (IBM10, n = 8) and 25 ml/60 min in group 2 (IBM60, n = 7). A 28 day follow-up is currently available for twelve dogs (IBM10 n = 7; IBM60 n = 5). The development of the peripheral blood mononuclear cell (PBMC) and granulocyte chimerism was tested weekly. Blood count, kidney and liver enzymes were monitored routinely. Results: All animals engrafted. One dog of the IBM10 group died at d+15 (infection) and was therefore not included into analysis. The median number of infused total nucleated cells were in IBM10 4.1*108/kg (range 2.3-6.0*108/kg) and in IBM60 3.2*108/kg (range 1.8-4.4*108/kg; p=0.4). The infused CD34+ numbers were median 3.2*106/kg (range: 1.2-10.0*106/kg; IBM10) and 3.6*106/kg (range: 1.5-6.8*106/kg; IBM60; p=0.7). Time of leukocyte recovery was median d+11 after IBMT in both groups (range: d+4 to d+11, IBM10; d+8 to d+14, IBM60; p= 0.5). Median leukocytes nadirs amounted to 0.2*109/l for IBM10 and 0.3*109/l for IBM60 (p= 0.08). The median duration of leukopenia (<1*109/l) were similar (6d, range: 4-11d, IBM10; 3-9d, IBM60) (p= 0.6). Median platelet nadir was 0*109/l for both cohorts (range: 0.0-7.0*109/l, IBM10; 0.0-1.0*109/l, IBM60). The period of thrombocytopenia (≤20.0*109/l) was significantly prolonged in the IBM60 group (median 10d, range) compared to 5d (range: 3-12d) in the IBM10 group (p=0.05). Donor PBMC chimerisms at d+7, d+14 and d+28 were median 22% (range: 8-34%), 50% (range: 29-53%) and 67% (range: 47-73%) in IBM10. The results of PBMC chimerism for IBM60 were 11% (range: 5-34%), 42% (range: 20-42%) and 59% (range: 44-66%) at these time points (p = n.s.). Donor granulocyte chimerisms of median 33% (range: 11-83%), 100% (range: 58-100%) and 100% (range: 82-100%) were detected at d+7, d+14 and d+28 after HSCT in IBM10, respectively. The granulocyte chimerism in IBM60 amounted to 34% (range: 3-87%), 96% (range: 94-100%) and 98% (range: 96-100%) at the above mentioned time points p=n.s. for all time points). Conclusion: Our data suggest that early granulocyte and PBMC engraftment is not influenced by modification of the HSC infusion rate. However, the period of thrombocytopenia seems to be prolonged following a 60 minutes application. Therefore, longer infusion times in an IBMT setting seem not to be beneficial following toxicity reduced conditioning regimen. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Minimal Residual Disease (MRD) By Either Flow Cytometry or Cytogenetics Prior to an Allogeneic Hematopoietic Cell Transplant (allo-HCT) Predicts Poor Acute Myeloid Leukemia (AML) Outcomes

Blood ◽

10.1182/blood.v126.23.3221.3221 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3221-3221

Author(s):

Lakshmikanth Katragadda ◽

Maxim Norkin ◽

Myron Chang ◽

Yunfeng Dai ◽

Jan S Moreb ◽

...

Keyword(s):

Flow Cytometry ◽

Complete Remission ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Cox Proportional Hazards Model ◽

Cell Transplant ◽

Poor Risk ◽

The Impact ◽

Count Recovery

Abstract Introduction: Persistent AML is a known risk factor for poor outcomes after allo-HCT. The impact of MRD in patients who achieve complete remission (CR) or CR with incomplete count recovery (CRi) has been less well studied. Methods: We retrospectively reviewed the records of AML patients who underwent allo-HCT in morphological remission (<5% myeloblasts and normal marrow cellularity) with or without blood count recovery between January, 2000 and January, 2014. Data was collected for variables known to impact the prognosis of AML patients (Table 1). MRD was defined as evidence of abnormalities associated with AML by either flow cytometry, cytogenetics or Fluorescence in situ hybridization (FISH). The impact of MRD identified at the time of allo-HCT on cumulative incidence of relapse (CIR), progression free survival (PFS), and overall survival (OS) was assessed in MRD+ and MRD- patients. Results: A total of 166 eligible patients were identified. The median follow-up among living patients is 46 months (range, 13-103).Thirty seven (22%) patients had evidence of MRD (13 by flow cytometry only, 17 by cytogenetics/FISH only and 7 by both). MRD was more common in patients with poor risk karyotype at diagnosis and CRi at the time of allo-HCT (Table 1). PFS (P= 0.0016), OS (P=0.002), and CIR (P=0.02) were all significantly worse in MRD+ patients (Figures 1& 2). In univariate analysis, MRD+ patients, assessed by flow cytometry had worse PFS (P=0.0216) and OS (P=0.0314) compared to MRD- patients. Similarly patients with evidence of MRD+ by cytogenetics/FISH had worse PFS (P=0.007) and OS (P=0.0031). In a multivariate cox proportional hazards model 1) any MRD positivity prior to allo-HCT, 2) poor-risk karyotype at diagnosis, and 3) CRi at allo-HCT independently predicted significantly poor PFS and OS. Only poor-risk karyotype was associated with a significant increase in CIR, while MRD positivity showed a trend towards higher CIR. Conclusion: MRD positivity prior to HCT by either flow cytometry or by cytogenetics/FISH independently predicts adverse AML outcomes. Table 1. Comparison of pre-transplant variables Covariate Label MRD + (N=37) MRD - (N=129) P-Value Age(years) < 40 8 (21%) 20 (16%) 0.708 40 - 59 20 (53%) 69 (54%) ≥ 60 10 (26%) 39 (30%) Karyotype risk Favorable/ Intermediate 19 (53%) 95 (74%) 0.011 Poor 18 (47%) 33 (26%) Timing of Allo-HCT 1st remission (CR1) 28 (74%) 97 (76%) 0.792 > CR1 10 (26%) 31 (24%) Allo-HCT after1st relapse(>CR1): duration of CR1 > 12 mo 31 (82%) 113 (88%) 0.285 ≤ 12 mo 7 (18%) 15 (12%) Secondary AML No 23 (60%) 78 (61%) 0.964 Yes 15 (40%) 50 (39%) Complete remission vs CRi CR 28 (74%) 110 (86%) 0.077 CRi 10 (26%) 18 (14%) Conditioning Regimen Ablative 24 (63%) 72 (56%) 0.449 Other 14 (37%) 56 (44%) Donor Type Matched sibling donor 12 (32%) 42 (33%) 0.887 Other 26 (68%) 86 (67%) Female donor: male recipient (FDMR) Other 28 (80%) 91 (78%) 0.844 FDMR 7 (20%) 25 (22%) Disclosures No relevant conflicts of interest to declare.

Download Full-text

Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.4821 ◽

2010 ◽

Vol 28 (11) ◽

pp. 1878-1887 ◽

Cited By ~ 324

Author(s):

Brian L. McClune ◽

Daniel J. Weisdorf ◽

Tanya L. Pedersen ◽

Gisela Tunes da Silva ◽

Martin S. Tallman ◽

...

Keyword(s):

Complete Remission ◽

Myelodysplastic Syndrome ◽

Cell Transplantation ◽

Older Patients ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Myelogenous Leukemia ◽

The Impact ◽

First Complete Remission ◽

Reduced Intensity

PurposeAcute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR).Patients and MethodsWe reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS).ResultsUnivariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and ≥ 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS.ConclusionWith these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Download Full-text

Perspectives on the Use of a Medium-Dose Etoposide, Cyclophosphamide, and Total Body Irradiation Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation: The Japanese Experience from 1993 to Present

Journal of Clinical Medicine ◽

10.3390/jcm8050569 ◽

2019 ◽

Vol 8 (5) ◽

pp. 569 ◽

Cited By ~ 2

Author(s):

Masahiro Imamura ◽

Akio Shigematsu

Keyword(s):

Stem Cell ◽

Complete Remission ◽

Conditioning Regimen ◽

Mortality Rates ◽

Term Survival ◽

Hematopoietic Stem ◽

Total Body ◽

First Complete Remission ◽

Medium Dose

The outcome for adults with acute lymphoblastic leukemia (ALL) treated with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) is poor. Therefore, allogeneic HSCT (allo HSCT) for adults aged less than 50 years with ALL is performed with myeloablative conditioning (MAC) regimens. Among the several MAC regimens, a conditioning regimen of 120 mg/kg (60mg/kg for two days) cyclophosphamide (CY) and 12 gray fractionated (12 gray in six fractions for three days) total body irradiation (TBI) is commonly used, resulting in a long term survival rate of approximately 50% when transplanted at the first complete remission. The addition of 30 mg/kg (15 mg/kg for two days) etoposide (ETP) to the CY/TBI regimen revealed an excellent outcome (a long-term survival rate of approximately 80%) in adults with ALL, showing lower relapse and non-relapse mortality rates. It is preferable to perform allo HSCT with a medium-dose ETP/CY/TBI conditioning regimen at the first complete remission in high-risk ALL patients and at the second complete remission (in addition to the first complete remission) in standard-risk ALL patients. The ETP dose and administration schedule are important factors for reducing the relapse and non-relapse mortality rates, preserving a better outcome. The pharmacological study suggests that the prolonged administration of ETP at a reduced dose is a promising treatment.

Download Full-text

Is Consolidation and/or Maintenance Treatment a Standard Therapy in Elderly AML in First Complete Remission?.

Blood ◽

10.1182/blood.v106.11.2775.2775 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2775-2775

Author(s):

Elise Corre ◽

Jean-Pierre Marie ◽

Ollivier Legrand

Keyword(s):

Complete Remission ◽

Elderly Patients ◽

Maintenance Therapy ◽

Induction Therapy ◽

P Value ◽

Consolidation Therapy ◽

Term Survival ◽

Postremission Therapy ◽

Wbc Count ◽

First Complete Remission

Abstract The treatment of elderly patients with acute myeloid leukemia (AML) is very disappointing. Studies have established that if half of the intensivity treated patients achieve complete remission (CR), the high rate of relapse within the first year jeopardize the long term survival. No clearly effective postremission therapy had been established. Therefore we retrospective analyzed 141 elderly patients (>60 yo) in first CR, to evaluate the effectiveness of postremission therapy, consolidation (3+7or 2+5) and/or maintenance (low dose AraC). All patiens received a 3+7 induction therapy. In these 141 patients DFS and OS at 4 years are respectively 14%, and 19%. According to the clinical status of the patient after induction, 20 (14%) patients did not receive therapy after induction, 30 (21%) patients received only maintenance therapy, 53 (38%) patients received only consolidation therapy, and 38 patients (27%) received both consolidation and maintenance therapy. These 4 groups were stratified according to age (< >70 yo) and WBC (< or > 30 x 109/l) (See Tables). The outcome of these patients receiving or not post induction therapy is shown in these Tables. Patients DFS at 4 years OS at 4 years Consolidation No consolidation P value consolidation No consolidation P value Outcome of patients receiving or not consolidation therapy in 4 groups stratified according to age and WBC count < 70yo and WBC< 30x109/l 19% 13% p=0.01 27% 13% p=0.0074 <70yo and WBC>30x109/l 26% 0% p=0.08 38% 0% p=0.05 >70 yo and WBC < 30x109/l 0% 30% p=0.001 6% 30% p=0.01 >70 yo and WBC> 30x109/l 2% 0% NS 4% 0% NS In patients > 70 yo and WBC < 30 x 109/l patients who received consolidation have a poorer prognosis than patients who did not because the mortality in first complete remission (mortality during consolidation) was high (25% versus 0% respectively, P=0.01). Patients DFS at 4 years OS at 4 years Maintenance No Maintenance p value Maintenance No Maintenance P value Outcome of patients receiving or not maintenance therapy in 4 groups stratified according to age and WBC count <70yo and WBC<30x109/ 17% 20% NS 22% 25% NS <70 yo and WBC>30x109/l 23% 14% p=0.05 32% 23% NS >70 yo and WBC<30x109/l 25% 5% p=0.01 25% 5% p=0.008 >70 yo and WBC >30x109/l 2% 0% NS 4% 0% NS In conclusion, in patients < 70 yo consolidation ± maintenance therapy (for DFS in patients with > 30 x109/l) improves the outcome of these patients (DFS and OS). In patients > 70 yo and with WBC < 30 x109/l maintenance therapy without consolidation, improves outcome. In these later patients (> 70 yo and with WBC < 30 x 109/l) consolidation therapy decrease outcome. In patients > 70yo and with WBC > 30 x 109/l, both consolidation and/or maintenance therapy does not improve outcome.

Download Full-text

Pretransplatation PET as Major Prognostic Discriminant in IGEV (ifosfamide, gemcitabine, vinorelbine and prednisone) Treated Patients with Relapsed/Refractory Hodgkin's Lymphoma (HL).

Blood ◽

10.1182/blood.v114.22.3707.3707 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3707-3707

Author(s):

Rita Mazza ◽

Stefano Luminari ◽

Massimo Magagnoli ◽

Michele Spina ◽

Teodoro Chisesi ◽

...

Keyword(s):

Complete Remission ◽

Fdg Pet ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Disease Status ◽

Response To Therapy ◽

High Dose ◽

Bulky Disease ◽

The Impact

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Impact of Previous Invasive Fungal Infections on the Outcome of Patients Undergoing Allogeneic Hematopoietic Stem Cells

Blood ◽

10.1182/blood.v128.22.5748.5748 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5748-5748

Author(s):

Gaetano Maffongelli ◽

Laura Cudillo ◽

Fabio Di Piazza ◽

...

Keyword(s):

Conflicts Of Interest ◽

Fungal Infections ◽

Conditioning Regimen ◽

P Value ◽

Period Range ◽

European Organization ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Post Transplant ◽

The Impact

Abstract Introduction: Outcome in allogeneic HSCT varies widely depending on disease type, stage, stem cell source, HLA-matched status and conditioning regimen. IFI is a possible complication of HSCT and a prior IFI increases the patient's risk for transplant related mortality due to the possibility of reactivation of the fungal infection. This study aimed to evaluate the impact of a previous IFI history on transplant outcome Methods: We retrospectively collected the clinical data of patients considered eligible for allogeneic HSCT during 2014 at the Rome Transplant Network (RTN), a JACIE accredited metropolitan transplant program established in Rome since 2006. The observation of patients was continued until 31 December 2015. The diagnosis of IFI were defined as possible, probable and proven as established by European Organization for Research and treatment of Cancer. Results: Twenty-one (37%) out of 57 eligible patients had an IFI episode before transplant: 6 of the episodes were proven, 4 probable and 11 possible. Overall, 10 (47%) pneumonia, 4 (19%) gastroenteritis, 3 sinusitis, 2 candida sepsis, 1 meningitis and 1 cutaneous abscess were registered. Five out of 21 patients (23%) died before HSCT versus 2 of 36 patients (5%) without previous documented IFI, [OR 5.31 95% CI 0.93- 30.40 , p value 0.06 Fisher Test], . A larger percentage of patients with past IFI waited HSCT over 6 months from the date of eligibility in comparison with those without previous IFI [43% vs 30% ; OR 1.87 95% CI 0.54-6.40 , p value 0.5 Yates test]; Sixteen (57%) out of 28 dead patients in the pre-transplant period have had a previous IFI episode vs 5(17%) out of patients alive [OR 6.4, 95% CI 1.89-21.68, p value: 0.004 Yates Test]. In the post-transplant period, only 6% of patients with a past IFI, experienced an engraftment in a time of < 15 days, vs 30% of patients without past IFI [OR 4.86 CI 95% 0,5-43,2, p value 0,2 Yates test]. In the post-transplant period, a IFI was diagnosed in 13 (26%) patients; ten (76%) out of 13 patients had a past IFI versus 9 (24%) of the patients without IFI.. [OR 7.87, CI 95% 1,8-34,2, p value 0,005 Yates test].Among the dead HSCT patients, those who had a previous IFI had a lower median survival [160 days (range 22- 480)] compared to patients without a previous IFI who died [196.5 days period (range 20-820)]. Conclusions: A previous IFI episode in the pre transplant period slow the accessibility to the transplant, adversely affects the engraftment, and is significantly associated with increased post-transplant mortality Disclosures No relevant conflicts of interest to declare.

Download Full-text