aclarubicin and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

This article describes a potential treatment for early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), a relatively rare and highly aggressive hematologic malignancy. A 59-year-old woman admitted to our hospital with enlarged cervical lymph nodes, weight loss, abnormal count, and morphology of peripheral blood cells was diagnosed with ETP-ALL according to morphology, immunology, cytogenetics, and molecular biology. The patient initially received two cycles of the VICP regimen, including vincristine, idarubicin, cyclophosphamide, and prednisone, and had a response with positive minimal residual disease (MRD). The patient was then given venetoclax plus the CAG regimen, including aclarubicin, cytosine arabinoside, and granulocyte colony-stimulating factor. After one cycle, the patient achieved complete remission with negative MRD and was eligible for allogeneic hematopoietic stem cell transplantation.

Topics: Aclarubicin; Cytarabine; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cells, T-Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Cytarabine; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction

Topics: Aclarubicin; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Decitabine; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Salvage Therapy; Survival Analysis

Acute lymphoblastic leukemia (ALL) patients who fail to acquire complete remission (CR) or who relapse after initial response have poor prognosis. At present there is no consensus as to the standard salvage therapy for these patients. In this study, we retrospectively evaluate safety and efficacy of a salvage regimen (CAGLP) consisting of G-CSF, low-dose cytarabine, aclarubicin, l-asparaginase and prednisone. Thirty-six patients were included with primary refractory (n=13) or relapse (n=23). The overall response rate (ORR) and CR rate were 86.1% and 63.9%, respectively. With a median follow-up of 34 months, the probability of overall survival (OS) at 2 years was 30%±10% and the disease-free survival (DFS) rate was 15%±8%. Treatment-related mortality was 5.6%. Our preliminary results indicated that CAGLP was feasible, safe and effective as a salvage reinduction chemotherapy for primary refractory and relapsed ALL patients.

Topics: Aclarubicin; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Salvage Therapy; Treatment Outcome; Young Adult

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Granulocyte Colony-Stimulating Factor; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

We treated 90 relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph(-)-ALL) patients with CAG regimen [cytarabine (10mg/m(2)/12h, days 1-14), aclarubicin (5-7 mg/m(2)/day, days 1-8), granulocyte colony-stimulating factor (200 μg/m(2)/day, days 1-14)], 82 relapsed/refractory Ph(-)-ALL patients were treated with increasing aclarubicin dose CAG (5-7 mg/m(2)/day, days 1-14, HD-CAG). 96 relapsed/refractory Ph(-)-ALL patients treated with Hyper-CVAD regimen (control group). After one therapy course, among all groups, there were no statistically significant differences with complete remission (CR) and overall response [OR, CR+partial remission (PR)] rates (P>0.05). In CAG group, CR and OR rates for T-ALL exceeded those for B-ALL (P=0.001, 0.007), while in HD-CAG and control groups, those were not statistically significantly different (P>0.05). CR and OR rates of CAG group for B-ALL were lower than control group (P=0.004, 0.012). Among all groups, there were no statistically significant differences with CR and OR rates for T-ALL (P>0.05). CAG had lesser adverse event than Hyper-CVAD. The overall survival at 3 years for all groups were similar. Efficacy of CAG regimen was similar in comparison to Hyper-CVAD for relapsed/refractory Ph(-)-T-ALL. HD-CAG could not improve efficacy than CAG regimen.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Remission Induction; Retrospective Studies; Salvage Therapy; Survival Rate; Vincristine; Young Adult

We treated 60 relapsed/refractory mixed-phenotype acute leukemia patients (MPAL-1) with increasing the aclarubicin dose in CAG regimen (HD-CAG, cytarabine (10 mg/m(2)/12 h, days 1-14), aclarubicin (5-7 mg/m(2)/day, days 1-14), granulocyte colony-stimulating factor (200 μg/m(2)/day, days 1-14). This was compared to 64 relapsed/refractory MPAL patients (MPAL-2) treated with DOAP regimen (daunorubicin, vincristine/vindesine, cytarabine and prednisone), 113 relapsed/refractory acute myeloid leukemia (AML) patients and 78 acute lymphocytic leukemia (ALL) patients treated with HD-CAG regimen. After one course, complete remission (CR) and overall response [OR, CR+partial remission (PR)] rates for MPAL-1 exceeded MPAL-2 (CR, 61.02% vs. 28.13%, P=0.000; OR, 72.88% vs. 34.38%, P=0.000), but these data were similar to AML and ALL (P>0.05). In MPAL-1 group, CR and OR rates of T-lymphoid+myeloid immunophenotype were higher than B-lymphoid+myeloid immunophenotype (CR, 81.82% vs. 44.12%, P=0.005; OR, 90.91% vs. 58.82%, P=0.009). The overall survival at 3 years in MPAL-1, MPAL-2, AML and ALL groups were 14.2%±6.8%, 14.1%±6.4%, 17.3%±5.0% and 15.0%±5.3% (P>0.05). Side effects were similar between HD-CAG and DOAP (P>0.05). HD-CAG regimen is efficacious for relapsed/refractory MPAL, especially for T+My patients.

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Daunorubicin; Dose-Response Relationship, Drug; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Recurrence; Retrospective Studies; Salvage Therapy; Treatment Outcome; Vincristine; Young Adult

Despite improvements in treatment, the prognosis of relapsed or primary refractory acute lymphocytic leukemia (ALL) remains poor, and outcomes are worse in older adults with the short first complete remission (CR). Attainment of the second CR by salvage therapy would improve the survival of these patients and may enable them to undergo curative treatment with allogeneic hematopoietic stem cell transplantation. The fact that there are diverse salvage protocols for these adult patients but without a striking CR-induction efficacy indicates that efforts are still needed to indentify new effective reinduction regimens. In this study, the CAG regimen (cytarabine, 10 mg/m(2) subcutaneously every 12 h on days 1-14; aclarubicin, 5-7 mg/m(2) intravenously daily on days 1-8; and concurrent granulocyte colony-stimulating factor, 200 µg/m(2) /day subcutaneously) was administered to 25 patients with relapsed or refractory ALL, including 11 T-cell ALL (T-ALL) and 14 B-cell (B-ALL) patients (age range, 11-61 years; median age, 26 years), to assess its efficacy as a salvage therapy. One course of the CAG regimen resulted in an overall response [CR or partial remission (PR)] rate of 64%, a CR rate of 56% and generally mild adverse effects. An overall response was observed in all 11 T-ALL patients (10 CR and 1 PR) and 35.7% of B-ALL patients (p = 0.0009). The significant treatment potential of CAG regimen for relapsed or primary refractory ALL, especially for T-ALL patients, described in this report would prepare them for a second CR to pursue longer survival.

Topics: Aclarubicin; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; China; Combined Modality Therapy; Cytarabine; Disease-Free Survival; Drug Evaluation; Drug Resistance, Neoplasm; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Retrospective Studies; Salvage Therapy; Treatment Outcome; Young Adult

Topics: Aclarubicin; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Daunorubicin; DNA; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Retrospective Studies; Vincristine

It is vital to develop effective therapy for children with acute lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer relapse with current protocols. Cellular drug resistance is thought to be an important cause of induction failure and relapse. We performed in vitro tests of bone marrow samples in 196 children with newly diagnosed ALL with a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic cell survival (LCS) rate for dexamethasone and prednisolone. For each single drug, patients were classified into two groups, sensitive or resistant, by median concentration of LD70 or LCS. When patients were classified into three groups by sensitivity to four drugs of DPAV (dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year event-free survival (EFS; 95% confidence intervals) of the super sensitive group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735 (0.609 to 0.863), and that of the relatively resistant group (RR; sensitive to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then investigated the relationship between the above four-drug sensitivity and the time of relapse. The SS and IS patients tended to maintain continuous complete remission, and RR patients tended to undergo induction failure and early and late relapse (P = .004). Initial white blood cell count, immunologic classification, and age were also predictive factors, but the patient numbers showed no statistical correlation between these factors and the four-drug sensitivity groups (SS, IS, and RR). When we took three groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In vitro drug sensitivity testing provides additional prognostic information about childhood ALL, and early detection of drug resistance at the time chemotherapy commences may provide a successful strategy for individualizing treatment, as the results indicate de novo resistance to front-line drugs and suggest alternative, second-line drugs.

Topics: Aclarubicin; Adolescent; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bleomycin; Bone Marrow; Cell Survival; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Etoposide; Follow-Up Studies; Humans; Infant; Infant, Newborn; Life Tables; Melphalan; Methotrexate; Mitomycin; Mitoxantrone; Neoplastic Stem Cells; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prognosis; Recurrence; Remission Induction; Tumor Cells, Cultured; Vincristine

We have previously detected by immunofluorescent assay that the cellular localization of nucleophosmin/B23 (NPM) shifts from the nucleolus to the nucleoplasm (NPM-translocation) after exposure of cells to multiple agents. In order to improve the quantification of the NPM-translocation, we have developed a digital imaging technique. Human Lo leukemia cells, MCF-7 breast carcinoma cells, and fresh human leukemia cells were exposed to anthracyclines or actinomycin D for 4 h. The degree of NPM-translocation was determined and presented as the localization index (LI). Control cells had a LI of about 10, which indicates that the majority of NPM was localized in nucleoli. The LI for drug-treated cells decreased in a dosage- and time-dependent manner. The effect of two classes of anthracycline (daunomycin and aclacinomycin A) and different types of intercalators (daunomycin and actinomycin D) had additive effects on induction of NPM-translocation. The imaging procedure was easily applied to fresh leukemia cells, thus providing useful information regarding drug effects on cancer cells.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cell Nucleolus; Dactinomycin; Daunorubicin; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Humans; Image Processing, Computer-Assisted; Leukemia, Monocytic, Acute; Nuclear Proteins; Nucleophosmin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tumor Cells, Cultured

Daunorubicin (DNR) is a major front-line drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Previously, we showed that in vitro resistance to DNR at diagnosis is related to a poor long-term clinical outcome in childhood ALL and that relapsed ALL samples are more resistant to DNR than untreated ALL samples. In cell line studies, idarubicin (IDR), aclarubicin (ACR) and mitoxantrone (MIT) showed a (partial) lack of cross-resistance to the conventional anthracyclines DNR and doxorubicin (DOX), but clinical studies in childhood ALL have been inconclusive about the suggested lack of cross-resistance. In the present study we determined the in vitro cross-resistance pattern between DNR, DOX, IDR, ACR and MIT in 48 untreated and 39 relapsed samples from children with ALL using the MTT assay. The relapsed ALL group was about twice as resistant to DNR, DOX, IDR, ACR and MTT as the untreated ALL group. Thus, resistance developed to all five drugs. We found a significant cross-resistance between DNR, DOX, IDR, ACR and MIT, although in some individual cases in vitro anthracycline cross-resistance was less pronounced. We conclude that IDR, ACR and MIT cannot circumvent in vitro resistance to DNR in childhood ALL. Clinical studies may still prove whether IDR, ACR or MIT has a more favourable toxicity profile than DNR.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Bone Marrow; Child; Daunorubicin; Dose-Response Relationship, Drug; Drug Resistance; Humans; Idarubicin; Mitoxantrone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Topics: Aclarubicin; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Etoposide; Humans; Leukemia, Myeloid, Acute; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Sixteen children with refractory hematological malignancies were treated with a combination of BH.AC, aclacinomycin-A, 6-MP and predonisolone (BH-AC.AMP protocol). They were ALL(6), ANLL(8), CML(1) and NHL(1). The CR ratio was 17% in ALL, 50% in ANLL, and blast crisis of CML was treated successfully but NHL failed in the induction remission. Major complications were vomiting, nausea, gastrointestinal bleeding, hematuria and hemorrhagic cystitis. More than 10 days or 120 mg/m2 administration of aclacinomycin-A was thought to induce more severe side effects.

Topics: Aclarubicin; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Drug Administration Schedule; Female; Humans; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lymphoma; Male; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Remission Induction