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Leukemias
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
More intensive treatment strategies, based on experiences from the treatment of children and young adults with Burkitt’s lymphoma, have resulted in the inclusion of fractionated high-dose cyclophosphamide, high-dose methotrexate, and cytarabine. These modifications led to improvements in the CR rates, ascribed to the high-dose components of the protocols, although it is difficult to assess which of the high-dose combinations is more important, and the optimal doses remain debatable. The best responses have been reported with the hyper-CVAD regimen, which includes hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine.45 The treatment of BCR-ABL1-positive ALL has been more effective with the addition of ABL1 TKIs to chemotherapy regimens.46,47 The treatment of BCR-ABL1-like ALL has also improved with the addition of TKIs, based on the ABL partner gene, to chemotherapy, with durable success reported with both ABL TKIs and JAK2 inhibitors, which I discuss under investigational therapy.35 The treatment of adults has improved following the successful pediatric models.48
Acute Lymphoblastic Leukaemia
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
More intensive treatment strategies, based on experiences from the treatment of children and young adults with Burkitt’s lymphoma, have resulted in the inclusion of fractionated high-dose cyclophosphamide, high-dose methotrexate and cytarabine. These modifications led to improvements in the CR rates, ascribed to the high-dose components of the protocols, although it is difficult to assess which of the high-dose combinations is more important and the optimal doses remain debatable. The best responses, in particular for patients with Burkitt-type ALL (FAB L3), have been reported with the hyper CVAD regimen, which includes hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine. In a study of 288 patients with adult ALL investigators in Houston reported a CR of 92% and a 5-year overall survival of 38%.
Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCN)
Published in Dongyou Liu, Tumors and Cancers, 2017
For patients with advanced-stage BPDCN, intensive chemotherapy regimens derived from the management of non-Hodgkin lymphoma (CHOP [cyclophosphamide/hydroxydaunomycin/vincristine/prednisone] or CHOP-like), acute lymphoblastic leukemia (ALL; hyper-CVAD [hyperfractionated/cyclophosphamide/vincristine/doxorubicin/dexamethasone] alternating with methotrexate and cytarabine), and AML may be utilized. CHOP-like regimens demonstrate a response rate of 86%, a median time to relapse of 9 months involving the bone marrow and central nervous system, and an overall survival rate of 25% after 24 months. More intensive, hyper-CVAD like regimens show a response rate of 90%, a median duration of response of 20 months, and a median overall survival rate of 29 months. For relapsed BPDCN, which often has a reduced response to previous chemotherapy, alternative drugs (e.g., L-asparaginase/methotrexate/dexamethasone) may be considered.
Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia
Published in Hematology, 2022
Zheng Shi, Yiqian Zhu, Jing Zhang, Baoan Chen
Unlike pediatric patients, adults and the elderly were characterized by poor tolerance to chemotherapy according to past experience. In order to improve this situation, a single-arm, phase 2 study (NCT01371630) was performed to explore the effect of Inotuzumab Ozogamicin plus mini-hyper-CVD. Mini-hyper-CVD, a modified version of standard hyper-CVAD with lower dose, referred to cyclophosphamide and dexamethasone reduced to 50%, methotrexate reduced to 25% and no anthracycline. In 59 R/R ALL patients aged 18–87 years, 78% responded, of whom 82% were negative for MRD. The 1-year RFS and OS rates were 40% and 46%, respectively [83]. Encouraging results were also reported in patients with newly-diagnosed Ph- ALL aged 60 years and over. All but one patient (98%) achieved responses, and estimated 3-year EFS and OS were 49% (32–64) and 56% (39–70), respectively [84].
Characteristic features of primary testicular lymphoma and survival trends: a multicenter clinical study
Published in Hematology, 2022
Yujiao Sun, Xueshen Yan, Hongguo Zhao, Zhongguang Cui, Yayun Wang, Shuxiang Sun, Xiaohan Ning, Hong Xu
Rituximab plus CHOP is one of the most commonly used therapy regimens to date. As is known, the outcome of CD20-positive nodal DLBCL has been improved significantly after the application of rituximab; however, rituximab cannot effectively penetrate the blood-testicle barrier, so its concentration is minimal in the testicles. Conflicts exist about the effective use of rituximab [3,15]. In 2018, a retrospective study of 32 cases from China found that bilateral intervention (contralateral RT or resection) could improve OS and PFS in the rituximab group [16], but in the other that did not use rituximab, patients who performed unilateral or bilateral intervention had a similar OS and PFS. In our retrospective study, we also found differences in the outcome between the R-CHOP and CHOP group, with a P-value >0.05 but <0.1 in the PFS and OS curves. Although we believe this is meaningful, it is also perhaps related to the small sample size of patients that received the CHOP regimen. Use of dose-intensive strategies such as hyper-CVAD are limited because of the usual demographic features of patients with PTL. In our study, only four patients received the hyper-CVAD regimen, illustrative of the limited use of dose-intensive strategies.
Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation
Published in Hematology, 2022
Wellington F. Silva, Mariane T. Amano, Luiza L. Perruso, Maria Gabriella Cordeiro, Renata Kiyomi Kishimoto, Aline de Medeiros Leal, Luciana Nardinelli, Israel Bendit, Elvira DRP Velloso, Eduardo M. Rego, Vanderson Rocha
Over these five years, patients were treated according to our local protocol, which allocated patients to a given regimen according to age and Philadelphia chromosome status. Philadelphia-positive patients received chemotherapy plus tyrosine-kinase inhibitor (TKI), following GRAAPH-2005 [18], Hyper-CVAD [19], or TKI plus corticosteroids [20], depending on their age and status performance. Patients were referred to alloHCT if they had not achieved major molecular remission (quantitative RT–PCR BCR-ABL1 < 0.1%) in bone marrow aspirate and they had a suitable donor as well as eligibility for the procedure. This option was discussed thoroughly with all patients, weighing the individual relapse risk against HCT-related toxicity and mortality. Philadelphia-negative patients were treated as follows: pediatric protocol BFM-based if they were young (aBFM, 2015-2017: ≤ 35 years old; 2018-2020: ≤ 50 years old) [21]; adapted GRAALL-SA1 (elderly-GRAALL) if they were older (> 50 years old) [22]. Before 2018, patients between 36–50 years received adapted Hyper-CVAD protocol (HCVAD) [23]. Rituximab was not available for CD20-positive ALL cases as it is not reimbursed in the public health Brazilian system. In the BFM-based protocol, from 2018 onwards, native E. coli asparaginase was replaced by peg-asparaginase. Chemotherapy regimens are detailed in the supplementary appendix.