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Bendamusutine plus rituximab (BR) regimen is one of the standard regimens for indolent B-cell lymphomas, yet the possibility of reduction of cycles of BR therapy without compromising therapeutic effects is not still uncovered. We retrospectively surveyed 57 cases including 40 follicular lymphoma cases who underwent BR regimen in our institute. The overall response (OR) rate and complete response (CR) rate were 86.0% (95% confidential interval (CI), 74.2-93.7) and 54.4% (40.7-67.6), respectively. Five-year overall survival (OS) and 5-years progression-free survival (PFS) were 76.8% and 45.7%, respectively. We then grouped the patients by the number of administered cycles of BR regimen. PFS was significantly longer in 41 cases of the later cessation group (cycle 4-6) than in 16 cases of the earlier cessation group (cycle 1-3) (p = 0.012, 5-years PFS; 46.8% vs. 35.2%, respectively), and both of OR and CR rate of the former was better than the latter (OR rate; 95.1% vs. 62.5%, p < 0.01, CR rate; 61.4% vs. 31.3%, p = 0.04). Interestingly PFS of twenty-one (36.8%) cases receiving just 4 cycles was longer than that of 20 cases who received five or 6 cycles (p < 0.01, 5-years PFS; 71.8% vs. 23.2%, respectively). Focusing on the group of four cycles, the 12 case with CR revealed longer PFS than seven cases with partial response (PR), and median PFS was not reached in CR cases and 16.9 months in the PR cases (p < 0.01). These results suggest that four cycles at least should be administered if possible, and the outcome of the patients who discontinued BR after four cycles was not inferior to that of the cases who received five or six cycles. In conclusion, discontinuation after four cycles may be permissible in some cases with complete response to BR regimen., (© 2021 John Wiley & Sons Ltd.)

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC., Methods: Forty-two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors., Results: Twenty-two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% [16/22]) was significantly superior to RECIST (36.4% [8/22]) (P = .017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut-off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates < 50% were independent predictors for relapse-free survival (hazard ratio [HR], 3.92; P = .044) and overall survival (HR, 14.08; P = .023)., Conclusions: PERCIST was more accurate in determining NAT's therapeutic effects for PDAC than RECIST. MTV reduction rates were independent prognostic factors for PDAC., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We evaluated the prognostic significance of the serum level of the soluble form of interleukin-2 receptorα (sIL-2Rα) and investigated its association with CD25 expression on tumor cells in diffuse large B-cell lymphoma (DLBCL). Three hundred and thirty-eight adult patients with newly diagnosed DLBCL were eligible for this retrospective study. 32.2% of patients were treated with CHOP-like regimen and 67.8% with R-CHOP-like regimen. CD25 expression on the surface of tumor cells was evaluated in 143 cases and its relationship with sIL-2Rα level was also investigated. Both overall survival (OS) and progression-free survival (PFS) were poorer in patients with higher sIL-2Rα, in both R-CHOP and CHOP groups. sIL-2Rα > 1,000 U/mL and performance status (PS) ≥ 2 were independently associated with poorer OS, and sIL-2Rα > 1,000 U/mL, age > 60 years, and ≥ 2 extranodal sites were independently associated with poorer PFS in the R-CHOP group. The sIL-2Rα level was higher in the CD25-positive group than in the CD25-negative group in stage 3 or 4 disease (p = 0.010). Multiple linear regression analysis showed CD25 expression to be independently correlated with sIL-2Rα levels. High sIL-2Rα is an important risk factor for survival in DLBCL treated with not only CHOP-like, but also R-CHOP-like regimens, regardless of the tumor's expression of CD25.

We retrospectively investigated pathological types, clinical backgrounds, treatments and prognoses in 726 adult patients with newly diagnosed malignant lymphoma in Gunma Prefecture. They consisted of 679 patients with non-Hodgkin lymphoma (B-cell type, 603; T- and NK-cell type, 76) of which 376 patients had diffuse large B-cell lymphoma (DLBCL) and 47 patients with Hodgkin lymphoma. When comparing the prognosis of DLBCL between patients receiving rituximab (R-CHOP group; n=212) and not using rituximab (CHOP group; n=126), both 3-year overall survival (73.5% vs 61.7%, p=0.010) and 3-year progression-free survival (65.1% vs 45.8%, p<0.001) were statistically better in the R-CHOP group compared to the CHOP group. Our results suggest that more than half of patients were DLBCL and the rituximab-containing regimen results in an improved prognosis for DLBCL patients.

Paclitaxel and carboplatin chemotherapy is reported to be a platelet-sparing drug combination. The objective of this study was to elucidate whether docetaxel with carboplatin has a similar platelet-sparing effect. This study investigated the time-course of the changes in the platelet count and the circulating concentration of thrombopoietin (TPO), a platelet growth factor, during combination chemotherapy consisting of carboplatin and docetaxel. Eleven patients with advanced lung cancer were enrolled; 8 receiving carboplatin and docetaxel (docetaxel group), and 3 receiving carboplatin and irinotecan (irinotecan group). The time-course profiles of the platelet count and the circulating TPO concentration were determined and compared between the two groups. The platelet count decreased significantly only in the irinotecan group, and on day 15 after therapy the thrombocytopenia was pronounced in comparison with that in the docetaxel group. The circulating TPO concentration remained almost constant in the irinotecan group, with no significant increases, while that in the docetaxel group was increased significantly on day 4 (p < 0.05), day 8 (p < 0.05), and day 15 (p < 0.01) after therapy. There was also a significant difference between the docetaxel group and irinotecan group with respect to circulating TPO concentration (p < 0.05). These results suggest that docetaxel might also have a platelet-sparing effect on the anti-platelet activity of carboplatin, mediated by levels of circulating TPO concentration.

A phase I study was conducted to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of gemcitabine and irinotecan combination therapy as second line treatment in patients with advanced non-small cell lung cancer (NSCLC). Twelve patients with measurable NSCLC (age range 46-74 years; 7 males, 5 females; performance status 0 = 4, 1 = 8) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was platinum-based without gemcitabine or irinotecan. Gemcitabine was administered at a fixed dose of 1,000 mg/m2 after irinotecan administration, and irinotecan was administered at doses from 50 to 125 mg/m2 with an increment of 25 mg/m2, both on day 1 and 8. Chemotherapy was repeated every 3 weeks. Grade 3/4 leukopenia occurred in three patients (25%), neutropenia in four (33%), anemia in one (8%), and thrombocytopenia in one (8%). Grade 3 nausea and vomiting was observed in three (25%), grade 2 diarrhea in one (8%), and liver dysfunction in one (8%). Other toxicities were mild. Two of the three patients at level 4 (irinotecan 125 mg/m2) experienced dose limiting toxicity: one patient experienced grade 4 leukopenia and neutropenia, and the other experienced treatment delay of more than 2 weeks. The objective response rate was 16.6% (2/12). The maximum tolerated dose in this combination therapy was gemcitabine 1,000 mg/m2 and irinotecan 125 mg/m2. The dose level of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 on day 1 and 8 of a 3-week cycle is recommended for a phase II study.

A randomized controlled study of patients with multiple myeloma was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rhG-CSF:KW-2228) in treating neutropenia induced by chemotherapy, and its influence on the dose intensity of, and response rate to, chemotherapy. As a rule, 3 courses of chemotherapy at intervals of 4 weeks were administered both to the untreated and KW-2228-treated groups. Among 98 eligible patients evaluated for neutrophil recovery, a markedly reduced duration of neutropenia was observed during each course in the KW-2228 treated group. No significant difference distinguished the two groups in terms of incidence or duration of infection. However, febrile neutropenia appeared only in the untreated group. There was no significant difference in terms of response rate or dose intensity. However, only patients in the untreated group withdrew from the study due to protracted neutropenia. These results demonstrated that KW-2228 is effective and safe, and has a significant effect on the acceleration of neutrophil recovery in patients with neutropenia induced by chemotherapy for multiple myeloma, and is useful for the completion of chemotherapy regimens.

The efficacy and safety of a new formulation of lenograstim (recombinant glycosylated granulocyte colony-stimulating factor) prepared by switching the stabilizer from human serum albumin (HSA) to gelatin was investigated for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia (AML). The results obtained in the study using the gelatin-containing formulation (gelatin-lenograstim) were retrospectively compared to those obtained from a placebo-controlled double-blind randomized study (AML-DBT) using the HSA-containing formulation (HSA-lenograstim). The median time of neutrophil recovery to > or = 1000/mm3 was significantly shorter in the gelatin-lenograstim group (14 days) than in the placebo group (21 days, P = .0001), and there was no significant difference between the gelatin-lenograstim group and the HSA-lenograstim group (14.5 days of AML-DBT, P = .5462). The incidences of febrile neutropenia were significantly reduced in the gelatin-lenograstim group (24/43, 55.8%) compared to the placebo group (58/64, 90.6%, P < .0001). The incidence of fever and antibiotic use was also significantly lower in the gelatin-lenograstim group (69.8% and 83.7%, respectively) than in the placebo group (92.2%, P = .0034, and 96.9%, P = .0285, respectively). However, between the 2 groups there were no differences in the number of patients who had infectious episodes. No serious adverse drug reactions ascribed to gelatin-lenograstim were encountered. These results demonstrate that gelatin-lenograstim exerted beneficial effects in the acceleration of neutrophil recovery and in the reduction of fever, febrile neutropenia, and antibiotic use, and its efficacy was equivalent to HSA-lenograstim. Therefore, we concluded that the gelatin-lenograstim formulation, which offers no risk of virus contamination and can be stored at room temperature, is more beneficial than the HSA-lenograstim formulation.

We studied the possibility of performing peripheral blood stem cell (PBSC) harvests during the course of ABVD therapy by adding G-CSF to the treatment regimen. Six patients with high-risk Hodgkin's disease (HD) (5 untreated cases with bulky mass and 1 relapsed case) received G-CSF (5 micrograms/kg) subcutaneously from day 8 to day 13 of their first course of ABVD treatment; the numbers of CD34+ cells and CFU-GM were monitored. PBSC harvests were performed on day 12 and day 13 of subsequent ABVD plus G-CSF treatment courses. For all patients tested, we were able to harvest CFU-GM (3.78 +/- 1.19 x 10(5) colonies/kg) for peripheral blood stem cell transplants (PBSCT) by performing 2 to 4 cycles. of apheresis, without any modification to the original ABVD protocol. These findings suggest that ABVD plus G-CSF therapy is a strong candidate for the treatment of patients with high-risk HD who may undergo autologous PBSCT.

Three patients with chronic myeloid leukemia (CML) in blastic transformation were treated with G-CSF plus middle dose cytosine arabinoside (Ara-C). G-CSF was administered (150 mg, s.c. or 300 mg, d.i.v./day) 24 hr prior to Ara-C (2-3 g/body, 6 hour d.i.v. for 2-5 days) and continued until the peripheral neutrophil count rose above 1,000/microlitre. As a supplement, VP-16 (80 mg/m2, for 2 days) was administered as warranted to control the growth of blastic cells. All 3 patients survived for more than 12 months with a favorable performance status. Normal karyotypes were detected in 2 of the patients after chemotherapy. One of those patients in paticular demonstrated normal bone marrow findings with the almost complete disappearance of the Ph-positive clone. In vitro cultures of peroxidase-negative CML blastic cells revealed that G-CSF stimulated the induction of blastic cells into the cell cycle and that blastic cell apoptosis was more pronounced in cells cultured with G-CSF plus Ara-C than with G-CSF or Ara-C alone. G-CSF plus middle dose Ara-C therapy appears to be a strong candidate for the treatment of CML in blastic transformation with a poor prognosis.

A 56-year-old woman was referred to Shizuoka General Hospital on April 17, 1992, because of progressive jaundice and massive pleural effusion. A thorough work-up revealed the diagnosis of advanced left breast cancer complicated with direct invasion of the thoracic wall, pleural carcinomatosis, multiple liver and bone metastases and obstructive jaundice due to the hilar mass. From a prognostic point of view, we scheduled the treatment course as follows. First, we treated the chief complaints. After emergency drainage and chemo-adhesive therapy of the pleural lesion, percutaneous biliary drainage and radiotherapy were done for obstructive jaundice, followed by internal drainage with self-expandable metallic stents. For the primary cancer of the left breast, standard mastectomy was performed following 57 Gy of radiotherapy. MPA was also administered because estrogen-receptor was positive on the histological examination of the resected specimen. To complete the multi-disciplinary treatment, we implanted a vascular access percutaneously via the left femoral artery and started intermittent hepatic arterial infusion chemotherapy on an outpatient basis. The patient was discharged on the 123rd hospital day and is well and active without any symptom 9 months thereafter.

Current understanding of molecular genetics enables the establishment of new categories based on pathogenesis. Philadelphia (Ph) chromosome-positive leukemia has been reclassified into two molecularly distinct subsets, and the leukemogenesis at the cell level might be linked to the molecular changes. Therefore, treatment for leukemia patients with Ph chromosome could be based on the molecular characteristics. In this review, we discuss the strategy of treating patients with Ph-positive acute lymphoblastic leukemia and the benefit of the combined modality of interferon and chemotherapy.

We report here a patient who was diagnosed as having acute lymphoblastic leukemia (ALL-L2) and colon carcinoma simultaneously and a successful operation for the colon carcinoma was performed preceded to the treatment of ALL. The patient was a 43-year-old male who presented with acute abdominal symptoms and was diagnosed as ALL by the hematological examination and as colon carcinoma (well differentiated adenocarcinoma, Borrmann II) by colon fiberscope. The patient was underwent sigmoidcolectomy for colon carcinoma and was received antibiotics as well as recombinant human granulocyte colony-stimulating factor (rhG-CSF), Approximately two weeks later, the patient received AdVP (Adriamycin, vincristine, and prednisolone) for ALL and achieved a complete remission. It might be possible for some leukemia patients manifesting acute abdominal symptoms to perform surgical approaches, since the prognosis of leukemia patients improved and supportive therapies, including an application of rh-CSF, have developed.

We report here a patient with acute lymphoblastic leukemia (ALL) in whom hypofibrinogenemia developed during chemotherapy. The patient was a 65-year-old female who was diagnosed as having common ALL, and she was treated with BHAC-DMPV (enocitabine: 160 mg, daunorubicin : 40 mg, 6-MP: 35 mg, prednisolone (PSL): 60 mg, and vincristine: 2 mg). Hypofibrinogenemia appeared promptly each chemotherapy, including PSL was given. To ascertain a correlation between hypofibrinogenemia and the drugs given in this patient, a trial administration of PSL was attempted during a complete remission state. The level of fibrinogen, in terms of the amount of antigen or coagulability, decreased during PSL treatment, although the levels of AT III, plasminogen, alpha 2PI.Plm complex, and FDP did not change. Thus, it is difficult to speculate that PSL induced destruction of leukemia cells and release of protease from the cells resulting in fibrinolysis and hypofibrinogenemia in this case. These findings also suggest that the administration of only PSL could induce hypofibrinogenemia.