Effectiveness of modified hyper-CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience.

Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol. We used hyper-CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T-cell ALL only) rather than standard hyper-CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper-CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty-six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5-year OS rate was 51.8% (95% CI (confidence interval): 45.1-57.8%). Modified hyper-CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5-year overall that is comparable to standard hyper-CVAD regimen.

Jalaeikhoo H ，Rajaeinejad M ，Keyhani M ，Zokaasadi M ，Dehghani Firoozabadi MM ... -  《Cancer Medicine》

Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen.

Hyperglycemia, which is not uncommon during the treatment of acute lymphocytic leukemia (ALL), has been shown to be an independent predictor of adverse outcomes among hospitalized patients with undiagnosed diabetes; it also may have the potential to affect leukemic cell proliferation through altered metabolism. The purpose of the current study was to determine the prevalence of hyperglycemia during induction chemotherapy for ALL using a regimen comprised of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and to determine its effect on survival, duration of disease remission, and treatment-related complications. Two hundred seventy-eight adult patients with previously untreated ALL who achieved a complete remission with the hyper-CVAD regimen were evaluated. Hyperglycemia was defined as > or = 2 glucose determinations of > or = 200 mg/dL during the first 30 days of induction chemotherapy. Induction chemotherapy was comprised of fractionated cyclophosphamide at a dose of 300 mg/m2 twice daily on Days 1-3, doxorubicin at a dose of 50 mg/m2 on Day 4, vincristine at a dose of 2 mg on Days 4 and 11, and dexamethasone at a dose of 40 mg on Days 1-4 and Days 11-14 (hyper-CVAD). Hyper-CVAD, given in odd-number courses (Courses 1, 3, 5, and 7), was alternated with methotrexate and cytarabine (MTX/Ara-C), given in even-number courses (Courses 2, 4, 6, and 8). MTX/Ara-C was comprised of MTX at a dose of 200 mg/m2 over 2 hours followed by 800 mg/m2 over 22 hours on Day 1, Ara-C at a dose of 3 g/m2 every 12 hours for 4 doses over 2 days (Days 2 and 3), and intravenous methylprednisolone given at a dose of 50 mg twice daily on Days 1-3. The complete remission duration (CRD), survival, and treatment-related complications were determined for patients with and without hyperglycemia; differences between the two groups were assessed using standard statistical methods. Hyperglycemia was found to occur in 103 patients (37%). Patients with hyperglycemia had a shorter median CRD (24 months vs. 52 months; P = 0.001) and a shorter median survival (29 months vs. 88 months; P < 0.001); they also were more likely to develop sepsis (16.5% vs. 8.0%; P = 0.03) or any complicated infection (sepsis, pneumonia, or fungal) (38.8% vs. 25.1%; P = 0.016) compared with patients without hyperglycemia. Patients with hyperglycemia during induction chemotherapy for ALL with the hyper-CVAD regimen were found to have a shorter CRD, experience a significant increase in overall mortality, and be at an increased risk for developing complicated infections.

Weiser MA ，Cabanillas ME ，Konopleva M ，Thomas DA ，Pierce SA ，Escalante CP ，Kantarjian HM ，O'Brien SM ... -  《CANCER》

Comparison of two different schedules of granulocyte-colony-stimulating factor during treatment for acute lymphocytic leukemia with a hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen.

Weiser MA ，O'Brien S ，Thomas DA ，Pierce SA ，Lam TP ，Kantarjian HM ... -  《CANCER》

Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia.

Kantarjian H ，Thomas D ，O'Brien S ，Cortes J ，Giles F ，Jeha S ，Bueso-Ramos CE ，Pierce S ，Shan J ，Koller C ，Beran M ，Keating M ，Freireich EJ ... -  《CANCER》

Role of Allogeneic HCT as Postremission Therapy for Transplant-Eligible Adult Lymphoblastic Leukemia/Lymphoma After Frontline Hyper-CVAD.

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with cytarabine and methotrexate (hyper-CVAD) is a commonly used regimen in adults with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Adult patients fit for pediatric-inspired protocols have an excellent outcome with chemotherapy alone. However, it is unclear whether patients receiving hyper-CVAD should undergo allogeneic hematopoietic cell transplantation (HCT) as postremission therapy. Our aim was to examine the role of HCT at first complete remission (CR1) in adult ALL/LBL after hyper-CVAD. Adult patients with newly diagnosed ALL/LBL receiving frontline hyper-CVAD from 2008 to 2018 were identified and records retrospectively extracted. A total of 85 patients were identified and included for further analysis. The median (range) age was 23 (14-68) years, and 56 (66%) were male. A total of 24 (28%) had adverse cytogenetics, and 48 (56%) had at least one risk factor. All patients received hyper-CVAD as induction; induction failure was seen in 10 (12%). A total of 38 patients continued the hyper-CVAD course, while the remaining 47 received HCT in CR1. Three-year event-free survival (EFS) and overall survival for the entire cohort were 51.4% and 61.6%, respectively. Median follow-up of alive patients was 39.9 (3.8-123.8) months. At multivariable analysis for EFS, induction failure was associated with worse outcome (hazard ratio [HR], 4.8; 95% confidence interval [CI] 1.7-13.7; P = .003), whereas HCT in CR1 improved outcome (HR, 0.42; 95% CI 0.18-0.97; P = .044). Furthermore, HCT in CR1 was the only prognostic factor for overall survival (HR, 0.3; 95% CI 0.11-0.85; P = .023). HCT at CR1 resulted in a favorable EFS and overall survival in ALL/LBL patients after hyper-CVAD frontline therapy. Given that hyper-CVAD is a widely used protocol for adult patients, further examination of this observation is warranted.

Damlaj M ，Snnallah M ，Bashir R ，Eddine IS ，Alahmari B ，Salama H ，Alaskar A ，Alhejazi A ，Alzahrani M ... -  《-》