Treatment Intensification of Traditional BFM Therapy with 3 Chemotherapy Blocks and Double Delayed Intensification (Protocol II) Improves Outcome in Infants with High Risk (HR) Acute Lymphoblastic Leukemia (ALL): Results of Two Consecutive AIEOP Studies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 871-871 ◽  
Author(s):  
Carmelo Rizzari ◽  
Maria Grazia Valsecchi ◽  
Paola De Lorenzo ◽  
Maurizio Aricò ◽  
Giuseppe Basso ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
High Dose Chemotherapy ◽  
P Value ◽  
High Dose ◽  
Treatment Intensification ◽  
Treatment Protocols ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Introduction: Cure rates of ALL in children aged less than one year (i.e. infants) at diagnosis are in the range of 35–40%. Encouraging results have been recently reported in infants by using intensified treatment, including high dose chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Aim: To evaluate the impact of the two treatment strategies adopted in the AIEOP ALL 91 and 95 studies on the outcome of ALL in infants. Patients and Methods: Fifty-two infants with ALL were enrolled between 1991 and 1999 in two consecutive studies, named AIEOP ALL 91 and ALL 95. Infants with an identified t(4;11) translocation had to be included in the high risk (HR) groups whilst those without this genetic abnormality could be treated in the intermediate (IR) or HR groups according to presenting features and treatment response. Patients belonging to the IR groups received a traditional BFM back-bone based treatment (protocols I, M and II), while those classified in the HR groups underwent an tensified treatment including induction (BFM protocol IA only, in study AIEOP ALL 91, and IA+IB in study ALL 95), consolidation with either 9 blocks of non-cross-resistant drugs (ALL 91) or 3 blocks followed by the 8-drug reinduction regimen - BFM protocol II - repeated twice (ALL 95). All patients were given a continuation phase (reinforced in HR patients of study ALL 95 by vincristine/prednisone pulses). Overall treatment duration was 2 years in both studies. Results: Infants in studies ALL 91 (n=21) and ALL 95 (n=31) had similar biological and clinical characteristics. The overall event-free survival (EFS) at 5 years was 45.0% (SE 7.0%). The EFS, after censoring for HSCT in 1st CR, was 38.1% (SE 11.4%) in ALL 91 and 51.6% (SE 9.9%) in ALL 95 (p-value=0.29). Patients treated in the IR arm of the two studies had a similar outcome. Better results were obtained in patients treated in the HR arm of ALL 95 study, where 9/17 chemotherapy-only patients and 3/4 HSCT patients are alive in CCR as compared to 1/7 and 0/2, respectively, in patients treated in the ALL 91 study. Discussion: These data show that full traditional BFM therapy intensified by 3 post-induction chemotherapy blocks and double protocol II (adopted in study ALL 95), is associated with a better outcome in infants with HR ALL.

HCT-CI Is Not a Useful Predictor for Non Relapse Mortality in Older Patients (>60 years old) Receiving RIC Transplant for AML or MDS

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4158-4158 ◽  
Author(s):  
Victor Noriega ◽  
Hugues de Lavallade ◽  
Victoria T Potter ◽  
Pramila Krishnamurthy ◽  
Judith C. W. Marsh ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Older Patients ◽  
Ferritin Level ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
The Impact ◽  
Igg Level

Abstract Abstract 4158 Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative procedure for patients of high-risk acute myeloid leukaemia (AML) and Myelodysplastic syndromes (MDS). The development of reduced intensity protocols (RIC) has expanded this treatment modality to older patients and to those with comorbidities. The development of the HCT-CI has been an important advance in attempting to more effectively assess patient′s fitness and likely non-relapse mortality (NRM); however its prognosis significance in a population of elderly patients remains uncertain. We evaluated the impact of HCT-CI and other factors that may enhance risk stratification in patients of advanced age receiving a RIC HSCT with alemtuzumab T-cell depletion. 85 consecutive patients aged >60 years who received a RIC HSCT for MDS and AML between January 2002 and December 2010 were retrospectively analysed, All patients received an FBC conditioning regimen (fludarabine 150mg/m2 iv, busulphan 8mg/kg oral or 6.4 mg/kg iv, alemtuzumab 100mg iv) followed by HSCT from an HLA identical sibling (n=19) or volunteer unrelated donors (n=66). Median age was 64 years (range 60–72), with 57/28 male/female. Diagnoses included AML with trilineage dysplasia (AML-TLD n=47), RAEB I/II (n=17), CMML (n=8) and RCMD (n=13),cytogenetics (high risk n= 22), IPSS risk divided patients in Low/Intermediate 1 risk (n=13), Intermediate 2 (n=11), High risk (n=6), AML (n=47). A survival analysis for NRM, overall survival (OS), disease free survival (DFS) was performed including pre-transplant HCT-CI (HCT-CI 0 n=20, HCT-CI 1–2 n=21 and HCT-CI >=3 n=43), ferritin level (<1500 mg n=43, >1500 n=42), number of courses of high dose chemotherapy (=<2 courses n=49, > 2 courses n=33), disease status pre-transplant (CR n=75, no CR n=10), CRP level (<10 n=34, >10 n=25), age >= 65 (<65 n=53, >65 n= 32), albumin median (albumin median = 42g/L), median Inmunoglobulin G (IgG, median = 9,85g/L) and median Inmunoglobulin M (IgM, median = 0,79g/L). At last follow up 60/85 patient had died (NRM, n=25, relapse n=35; median follow-up, 3.5 years, range 0.3–9.5). HCT-CI score showed no statistically significant impact on 2-year NRM (27 %, 40% and 42% in patients having an HCI-CI score of 0, 1–2 and > =3 respectively, p=0.522, Figure) and 3-year NRM (27%, 52% and 49% respectively) or on 2-year OS (40 %, 39% and 29% in patients having an HCI-CI score of 0, 1–2 and > =3 respectively, p=0.577). Ferritin level, number of courses of high dose chemotherapy, CRP level, age >= 65, albumin level and IgM had not statistically significant impact on NRM or OS, while there was a trend of better outcome for patients with higher IgG level (2 and 3-year NRM 26% and 35% vs 53% and 61%, p=0,090, Figure 1). Of note -and as expected- patients in CR at the time of transplant had a better outcome (2 year OS of 38% vs 0%, p=0,008), and high risk cytogenetics was associated with poorer 2-year OS (41% vs 15% (p=0,006). In summary HCT-CI does not best identify patients at higher risk of NRM in patients older than 60 years receiving an alemtuzumab T-cell depleted RIC allo HSCT for AML or MDS while there is a trend toward worse NRM in patients with lower IgG level; this suggests that poorer humoral immunity before transplant might reflect higher risk of NRM although the underlying mechanism remains to be further investigated. Figure 1. Figure 1. Disclosures: No relevant conflicts of interest to declare.

Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma

Cancer ◽  
2006 ◽  
Vol 106 (11) ◽  
pp. 2327-2336 ◽  
Author(s):  
Emer O. Hanrahan ◽  
Kristine Broglio ◽  
Deborah Frye ◽  
Aman U. Buzdar ◽  
Richard L. Theriault ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Breast Carcinoma ◽  
Randomized Trial ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Primary Breast Carcinoma ◽  
Hematopoietic Stem ◽  
Stem Cell Support ◽  
Cell Support

scholarly journals Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children’s Oncology Group

2017 ◽  
Vol 35 (23) ◽  
pp. 2700-2707 ◽  
Author(s):  
Kristina K. Hardy ◽  
Leanne Embry ◽  
John A. Kairalla ◽  
Shanjun Helian ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Corticosteroid Treatment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Outcomes ◽  
Leucovorin Rescue ◽  
B Lineage ◽  
The Impact

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.

Intensification of Chemotherapeutic Regimens and Hematopoietic Stem Cell Transplantation Are Responsible for Improved Overall Survival in Adult Acute Lymphoblastic Leukemia in a Single Center Over the Last Forty Years

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4227-4227
Author(s):  
Estrella Carrillo ◽  
Nancy Rodriguez ◽  
Juan Francisco Dominguez ◽  
Jose Gonzalez ◽  
Jose Francisco Falantes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Male Gender ◽  
Hematopoietic Stem ◽  
System Involvement ◽  
The Impact

Abstract Abstract 4227 Background Acute lymphoblastic leukemia (ALL) of adults is an infrequent and heterogeneous disease according to presentation pattern, prognosis and treatment. It is widely assumed that age above 30 years, leukocytosis >25 ×109/L, central nervous system involvement and specific cytogenetic disorders such as t(9;22) or MLL rearrangement entail bad prognosis. There are controversial studies on the impact of intensification chemotherapy and hematopoietic stem cell transplantation (HSCT) on survival of these high-risk groups. Aims To identify biological, clinical and prognostic characteristics in adult ALL patients diagnosed and followed in a single center throughout 40 years as long as the impact on clinical outcome of different consecutive therapeutic approaches, including HSCT, in different periods. Patients and methods Throughout 1970 to 2011, 230 patients were prospectively registered and retrospectively analyzed. Most patients accomplishing pre-determined criteria received treatment according to PETHEMA or locally developed therapeutic protocols (including HSCT in relapse high-risk patients, since 1978). Critical variables at diagnosis such as age, gender, phenotype (from 1978), cytogenetic (from 1999), white blood cells count (WBC) and central nervous system involvement, were analyzed. Response to induction chemotherapy, relapse rate (RR) and 5 year overall survival (OS) were analyzed in the whole cohort and separately by decade when treatment protocols were different. The clinical impact of HSCT was analyzed on a subgroup of patients homogeneously treated since 1994. Statistical analysis was performed by mean of Chi-square and Kaplan Meier tests, as appropriate. Outcome Table 1 summarizes the presentation pattern and its prognostic value. At diagnosis features such male gender, age above 30 years, central nervous system involvement, leukocytosis >10×109/L, MLL rearrangement, t(9:22) and complex karyotype entailed a worse prognosis. For the whole cohort the 5 years OS was 30%. CR was achieved in 73% and the RR was 38%. 5 years OS has improved by decades: 11% in the 70s, 24% in the 80s, 30% in the 90s, and 41% in XXI century (p<0,01). Patients selected for intensive chemotherapeutic protocols achieved a similar CR rate in each decade (nearly 80%) while the RR decreased through the years (70s: 68%, 80s: 44%, 90: 42%, 00–11: 25%; p<0,01). Patients treated with chemotherapy plus HSCT achieved in 5 years (from 1994) an OS of 69% in comparison with the 30% obtained in those patients who only received chemotherapy (p<0,01). Conclusion Male gender, age above 30, WBC >10×10e9/L, t(9;22), MLL-rearrangement, complex karyotype and CNS involvement conferred poor prognosis in adult ALL. Intensification of chemotherapeutic regimens produced a progressive decrease in relapse rate, leading to an improvement in overall survival over the years. HSCT seems to partially overcome the poor prognosis related to high risk factors. Disclosures: Perez-Simón: Janssen-Cilag: Patents & Royalties.

scholarly journals Bone Marrow and Peripheral Blood Hematopoietic Stem Cell Transplantation: Focus on Autografting

2000 ◽  
Vol 46 (8) ◽  
pp. 1239-1251 ◽  
Author(s):  
Roy D Baynes ◽  
Caroline Hamm ◽  
Roger Dansey ◽  
Jared Klein ◽  
Lucinda Cassells ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Non Hodgkin Lymphoma

Abstract This review focuses on certain of the principles involved in high-dose chemotherapy and radiation therapy along with autologous hematopoietic stem cell transplantation for the treatment of certain malignancies. In addition, the evidence, wherever possible based on randomized data, for the application of this approach in certain malignancies is reviewed. The malignancies highlighted include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease, and breast cancer.

Autologous peripheral-blood progenitor-cell support following high-dosechemotherapy or chemoradiotherapy in patients with high-risk multiple myeloma.

1996 ◽  
Vol 14 (4) ◽  
pp. 1306-1313 ◽  
Author(s):  
G Marit ◽  
C Faberes ◽  
J L Pico ◽  
J M Boiron ◽  
J H Bourhis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Autologous Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Median Response ◽  
Cell Support

PURPOSE The aims of the current study were to evaluate in patients with high-risk multiple myeloma (MM) the feasibility and usefulness of high-dose chemotherapy or chemoradiotherapy followed by hematopoietic stem-cell support with autologous peripheral-blood progenitor cells (PBPC) harvested after high-dose cyclophosphamide (HDCYC). PATIENTS AND METHODS Seventy-three patients with high-risk MM were entered onto the study. Before the procedure, all patients had received HDCYC to collect PBPC by leukapheresis. One patient died of infection after HDCYC. All other patients subsequently received high-dose melphalan (HDM) (140 mg/m2) either alone (n = 1) or associated with either busulfan (16 mg/kg; n = 4) or total-body irradiation (TBI) (8 to 15 Gy; n= 67). In addition, three of the latter patients received cyclophosphamide (120 mg/kg). Thereafter, PBPC were reinfused either alone in 61 patients or together with back-up bone marrow cells in 11 patients in whom the granulocyte-macrophage colony-forming unit (CFU-GM) cell content of the leukapheresis was low. RESULTS One patient died of acute cardiac failure after reinfusion of PBPC; three patients did not respond after autologous blood progenitor cell transplantation (ABPCT), while the other 68 patients achieved either a complete response (CR; n = 32) or partial response (PR; n = 36). Thirty-six patients relapsed or progressed after a median response duration of 14.5 months (range, 3 to 43) and 19 of these subsequently died. Four other patients died while still responsive of lung cancer (n = 1) or infection (n = 3). The remaining 28 patients are currently alive and still responding with a median follow-up duration of 27 months (range, 6 to 66). The 3-year probability of survival was 66% +/- 12% (95% confidence interval [CI] after ABPCT and 77% +/- 51% (95% CI) from diagnosis. CONCLUSION High-dose chemotherapy or chemoradiotherapy followed by autologous PBPC support in MM is feasible and efficient. Further studies are needed to confirm these encouraging, although preliminary, results and to compare this technique with other therapeutic strategies.

Allogeneic immunotherapy by hematopoietic stem cell transplantation (ASCT) after reduced intensity conditioning (RIC) following high-dose chemotherapy for patients with acute myeloblastic leukemia (AML) in first complete remission (CR1): Reduced toxicity

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7098-7098
Author(s):  
D. Blaise ◽  
R. Tabrizi ◽  
C. Faucher ◽  
M. Mohty ◽  
J. Bay ◽  
...  
Keyword(s):  
High Risk ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
Probability Estimates ◽  
White Blood Cell Counts ◽  
Reduced Toxicity

7098 Background: RIC-based ASCT can be used after intensive chemotherapy in pts with CR1AML(Blaise, Cancer, 2005). Initial disease control was high and was not related to selection bias (Mohty, Leukemia, 2005).Here, we investigated if this control was maintained after a long follow-up. Methods: 37 pts (age: 51 (26–60)) with high risk clinical characteristics (70%) (Age = 50 (N=22, 59%); severe comorbidity (30%)) and/or poor risk leukemic features (65%) (Cytogenetics (35%); 2 induction courses (27%); secondary leukemia (11%), High white blood cell counts(14%) or partial remission (3%)) were treated. After CR1, pts received at least either 1 course of high dose cytarabine (24 g/m2) and anthracycline (HIDAC: N=21) or HIDAC + 1 course of. melphalan (140 mg/m2) (HDMEL) with auto-SCT Pts (HIDAC +HDM N=16). All pts were then scheduled to receive ASCT prepared with RIC (fludarabine (180 mg/m2), busulfan (8 mg/kg), Thymoglobulin (2.5 to 10 mg/kg)) followed with BMT (28%) or PBSC (72%). Results: With a Median follow-up of 3 years (16–70 mths). 15 pts experienced aGVHD (grade 2–4 aGVHD cumulative incidence (CI):22% (9–35). 10 and 14 pts presented a limited and extensive cGVHD respectively (CI cGVHD:65 % (50–80). 3 deaths were attributed to non-relapse causes (NRD) (AGVHD: 1; CGVHD: 2° (NRD CI: 8% (0–17). In all, 9 pts relapsed at 5 mths (2–19) (24% (9–35). Relapse was associated with the absence of cGVHD (cGVHD: 8 (0–19), no cGVHD 44% (12–76), p=.05). 25 pts are still alive in CR1 for overall survival and leukemia-free survival (LFS) probability estimates at 4 years of 65 % (48–79%) and 66% (49–80%) respectively. When restricting the analysis to the 33 pts evaluable for cGVHD, cGVHD remained the only independent risk factor positively influencing LFS (cGVHD: 81% (59–92); no cGVHD (56% (27–81), p=.05) Conclusions: We conclude that RIC Allo-SCT preceded by adequate prior intensive chemotherapy might offers a relatively low NRD while exerting a sustained leukemia control even in high risk pts deserving prospective evaluation against standard strategy of conventional Allo SCT. No significant financial relationships to disclose.

High-risk Neuroblastoma: Poor Outcomes Despite Aggressive Multimodal Therapy

2021 ◽  
Vol 17 ◽  
Author(s):  
Adil Abdelhamed Abbas ◽  
Alaa Mohammed Noor Samkari
Keyword(s):  
High Risk ◽  
Multimodal Therapy ◽  
Treatment Strategies ◽  
Low Risk ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Clinical Behavior ◽  
Frequent Relapses ◽  
Recent Developments ◽  
Poor Outcomes

: Neuroblastoma (NBL) is a highly malignant embryonal tumor that originates from the primordial neural crest cells. NBL is the most common tumor in infants and the most common extracranial solid tumor in children. The tumor is more commonly diagnosed in children of 1-4 years of age. NBL is characterized by enigmatic clinical behavior that ranges from spontaneous regression to an aggressive clinical course leading to frequent relapses and death. Based on the likelihood of progression and relapse, the International Neuroblastoma Risk Group classification system categorized NBL into very low risk, low risk, intermediate risk, and high risk (HR) groups. HR NBL is defined based on the patient's age (> 18 months), disease metastasis, tumor histology, and MYCN gene amplification. HR NBL is diagnosed in nearly 40% of patients, mainly those > 18 months of age, and is associated with aggressive clinical behavior. Treatment strategies involve the use of intensive chemotherapy (CTR), surgical resection, high dose CTR with hematopoietic stem cell support, radiotherapy, biotherapy, and immunotherapy with Anti-ganglioside 2 monoclonal antibodies. Although HR NBL is now better characterized and aggressive multimodal therapy is applied, the outcomes of treatment are still poor, with overall survival and event-free survival of approximately 40% and 30% at 3-years, respectively. The short and long-term side effects of therapy are tremendous. HR NBL carries a high mortality rate accounting for nearly 15% of pediatric cancer deaths. However, most mortalities are attributed to the high frequency of disease relapse (50%) and disease reactiveness to therapy (20%). Newer treatment strategies are therefore urgently needed. Recent discoveries in the field of biology and molecular genetics of NBL have led to the identification of several targets that can improve the treatment results. In this review, we discuss the different aspects of the epidemiology, biology, clinical presentations, diagnosis, and treatment of HR NBL, in addition to the recent developments in the management of the disease.

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