bluuebunny/crossref_metadata_2025_split huggingface dataset:
G-CSF Supported CHOP-14 with Rituximab in Patients <60 Years with High-Risk Diffuse Large B Cell Lymphoma (DLBCL).
Authors: Bernell Per , Hedlund Anette , Bjorkholm Magnus 
Published: October 2019

Introduction: During recent years studies have shown that elderly patients with aggressive lymphoma may benefit from dose-intensified chemotherapy (CHOP-14). In addition, the addition of rituximab (R) to CHOP-21, seems to improve response rates and survival in elderly patients and younger patients with low and low/intermediate risk factors. Given these promising results we early decided to use G-CSF supported R-CHOP-14 in patients < 60 years with previously untreated DLBCL and risk factors.
Patients and methods: Between March 2000 and June 2003, 25 consecutive and previously untreated patients with CD20+, stage II–IV DLBCL and ≥ 1 risk factor (IPI) were included. HIV+ patients and patients with CNS involvement were not eligible. The median age was 56 years (range 27–60). The CHOP regimen (6–8 cycles) was delivered every 14 days with R (375mg/m2) iv on day 1. G-CSF (300ug/day) was given sc from day 5 to day 13 or until an absolute granulocyte count >4.0x109/l. Re-staging studies were routinely performed every two cycles. Non-responding patients were planned to receive MIME chemotherapy followed by high-dose therapy and autologous stem cell support (ASCS). Four patients were given local radiotherapy to previous bulky disease.
Results: Seven (28%) patients had an IPI score of 1 and 72% IPI 2 or 3. 23/25 (91%) had elevated S-LDH, 12/25 (48%) had bulky disease and 14/25 (56%) had an extranodal lymphoma manifestation. 17/25 (68%) of tumors were positive for bcl-2 (immunohistochemistry). 22/25 (88%) patients achieved a CR. One SD patient (IPI 3) died from progressive disease and two patients with PR and SD after 4 courses received dose-escalated MIME chemotherapy and BEAM high-dose therapy with ACSC and remain in CR. After a median observation time of 32 months (range 21–37 months) 4 (3 with IPI 3) of 22 CR patients have relapsed following R-CHOP. Two (both IPI 3) of relapsing patients died from lymphoma. R-CHOP was delivered on day 15 in 83% of cycles. Grade 3–4 neutropenia and thrombocytopenia were observed in 80% and 16% of patients, respectively. Five patients developed neutropenic fever and pneumonia was diagnosed in additional 3 patients. Non-hematological toxicity was in general mild. Grade 3 or 4 adverse events related to the infusion of R were not observed.
Conclusion: G-CSF supported R-CHOP-14 immunochemotherapy is feasible, safe and effective in young patients with advanced aggressive DLBCL and risk features. Innovative treatment approaches are needed for non-responding and relapsing patients.
Rituximab Plus Dose Enhancement and Biweekly Administration of CHOP for Newly-Diagnosed Patients with Diffuse Large-B-Cell Lymphoma.
Authors: Javier Francisco , Ríos E. , Almagro M. , Durán-Cabral J.M. , Rodríguez J.N. , Durán-Nieto S. , Bergua J. , Martino L. , Romero A. , Martín-Reina M.V. , Gil J.L. 
Published: October 2019

Abstract
Introduction: Rituximab plus CHOP every 3 weeks is associated with a increase in the survival of elderly patients. Dose intensification and dose compression with G-CSF support may provide an advantage compared with standard-dose CHOP.
Purpose: To evaluate the efficacy and safety of Rituximab plus CHOP with increased dose of cyclophosphamide and shortened intervals between chemotherapy courses in newly-diagnosed patients with diffuse large-B-cell lymphoma.
Therapeutic scheme: Rituximab 375 mg/m2 (d1), cyclophosphamide 1.500 mg/m2 (d1), vincristine 1.4 mg/m2 maximum 2 mg (d1), adriamycin 50 mg/m2 (d1) and prednisone were given. G-CSF (5–10 μg/kg) was added on days 3 to 11 in each course. Six to 8 courses were applied at 14-day intervals.
Results: Between january 2002 and may 2005 twenty eight patients, from seven institutions, were included in this study and received 187 courses. Their median age was 48 years (19 to 59 years). The four last patients have not yet finished their treatment and were not evaluable for response. All patients exhibited alopecia and acceptable myelosupression. Thirteen episodes of fever were reported. Among 24 evaluable patients ORR was 83.3% (70.8% CR and 12.5% PR). With a median follow-up of 11 months (range 4–42) the OS and EFS at 30 months is 83% and 75%, respectively.
Conclusions: The administration of Rituximab plus CHOP every 14 days with enhanced dose of cyclophosphamide is safe. The toxicity is mainly hematological, but can be surmounted with the use of G-CSF and EPO. Recruitment of more patients and longer follow-up are required to confirm these results.
Primary Bone Lymphoma. A Single Center Experience.
Authors: Bouzani Maria , Gigantes Stavros , Rontogianni Dimitra , Violaki Vasiliki , Karmiris Themis , Apostolidis John , Mpakiri Maria , Sotiropoulou Anastasia , Nikiforakis Emmanuel 
Published: October 2019

Abstract
Introduction. Primary Bone Lymphomas [PBL] are rare extranodal non Hodgkin’s Lymphomas [NHL] constituting about 5% of all extranodal NHL. In this study we present our experience from a retrospective analysis of patients with PBL; we have assessed the patient characteristics, response to therapy and outcome.
Patients - Methods. From a population of 600 newly diagnosed patients with NHL who have been registered to our Unit between 1990 and 2004, 18 [ 3% ] have been classified as PBL. Apart from patient characteristics and clinical course, 12 cases were studied with immunohistochemistry for expression of antigens associated with different stages of B-cell differentiation. The median age of the patients [12 men, 6 women, M/F ratio 2/1] was 54 years (range 32 – 83). The stage of the disease was evaluated as I in 12 patients (66 %), II in one (6%), and IV in five patients (28%). The histology was that of a diffuse large -B-cell lymphoma in 17 cases [94%] while one patient [6%] had lymphoplasmacytoid lymphoma. The most common site of involvement was the axial skeleton (13/18, 72%), followed by the long bones of the extremities (5/18, 27%). All studied tumors revealed a germinal center [ G-C] immunophenotype signature [bcl−6 +], but only 4 of 12 [33%] confirmed their G-C origin [bcl-6+CD10+].
Results: Sixteen patients were treated with an anthracycline based chemotherapy regimen with [14] or without [2] radiotherapy [RT]. Only one patient was treated with RT alone, while one patient denied treatment. Fifteen patients (88%) achieved complete remission, one (6%) partial remission, and one patient (6%) had progressive disease to first line therapy with a CHOP-like regimen. Five patients (30%) experienced relapse; in three cases the relapses involved the CNS. Finally, 16 patients remain alive: 14 in CR [10 (60%) in 1st, 4 (23%) in 2nd CR], and one (6%) with active disease. Two patients (11%) have died, both with CNS disease. One patient survives without recieving treatment. With a median follow-up time of 47 months (range 8– 150), the 6 year actuarial overall and disease free survival was 72% and 52% respectively.
Conclusions: PBL are rare extranodal NHL. They mostly involve the bones of the axial skeleton. The vast majority of them present with a germinal center immunophenotypic profile. The response rate is high (88%). However, the disease recurs in one third of the cases, most often in the CNS.
A Phase II Study of the Combination of Topotecan, Ara-C, Cisplatin and Prednisolone (Toposhap) for Slavage of Primary Refractory and Relapsed Patients with Lymphoid Malignancies.
Authors: Giglio Auro del , Dantas André A.P.H. , Burgos Ana Rita M. 
Published: October 2019

Abstract
Introduction: Topotecan has activity in several hematological malignancies. We have previosuly described a phase I trial of the combination of Topotecan, Cisplatin, Ara-C and Prednisolone (TOPOSHAP) (Acta Haematol. 2004;112(3):121–5). In this phase I study the recomended doses were Topotecan 1,0 mg/m2/d, IV, given on days 1 to 3, Cisplatin 25 mg/m2/d, IV, on days 1 to 3, Ara-c 500 mg/m2, IV, on day 4, prednisolone 250 mg, IV, on days 1 to 4.
Patients and Methods: We treated 22 patients (19 to 73 years old) with primary refractory or relapsed Acute lymphoblastic leukemia (ALL), Non-Hodgkin’s Lymphoma (NHL) or Hodgkin’s disease (HD), with measurable disease, with the TOPOSHAP regimen in the aforementioned doses. Tumor reponse was evaluated after the second cycle of this regimen.
Results: Fifty four cycles of chemotherapy were given, ranging from 2 to 6 per patient. One patient died before completing the second cycle of chemotherapy. In the 19 evaluable patients we observed a response rate of 53% (5 CR and 6 PR). All patients had grade IV myelotoxicity and 8 required dose reduction. Seven patients had febrile neutropenia and 3 had mucositis, 2 had diarrhea and 1 had WHO grade 1 renal insuficiency.
Conclusion: We conclude that the TOPOSHAP regimen is an active regimen for the salvage of refractory or relapsed patients with hematological lymphoid malignancies.
Randomized Comparison of Cladribine Containing Regimens and COP in Previously Untreated Patients with Small Lymphocytic, Marginal Zone and Follicular Lymphoma.
Authors: Kalinka Ewa , Wajs Jaroslaw , Sulek Kazimierz , Robak Tadeusz , Blasinska-Morawiec Maria , Sawczuk-Chabin Joanna , Ceglarek Bernadetta , Konopka Lech , Centkowski Piotr , Seferynska Ilona , Warzocha Krzysztof 
Published: October 2019

Abstract
The aim of the study was to comparatively assess first-line treatment with cladribine alone or in combination with cyclophosphamide (CCR, cladribine-containing regimens) and COP (cyclophosphamide, vincristine, prednisone) in different subtypes of low-grade lymphoma. End points were complete remission (CR), overall response rate (ORR), incidence of chemotherapy-related side effects as well as freedom from progression (FFP) and overall survival (OS). From June’2000 to June’2005, 178 previously untreated patients (pts) were randomly allocated to receive 6 monthly courses of either CCR or COP in 17 centers in Poland. This analysis included 107 pts who have completed scheduled chemotherapy, including 45 pts with small lymphocytic (SLL, median age=64 years), 26 marginal zone (MZL, median age=58 years) and 36 follicular (FL, median age=65 years) lymphoma. Compared to COP, CCR induced higher CR rates in all treated groups (65% vs 15%, p=.005; 57% vs 10%, p=.02; 58% vs 12%, p=.03, respectively) but differences in ORR were not significant (92% vs 69%; 92% vs 60%; 79% vs 62%, respectively). Incidence of side effects did not differ significantly in CCR- as compared to COP-treated pts, e.i. infections (10% vs 7%; 14% vs 20%; 15% vs 0%, respectively), myelosuppression (31% vs 7%; 21% vs 20%; 30% vs 0%, respectively), and non-hematological adverse events (10% vs 14%; 7% vs 30%; 7% vs 22%, respectively). With a median follow-up of 12 months, median FFP was superior in CCR- as compared to COP-treated treated pts with SLL (43 vs 12 months, log-rank p<.03) or MZL (37 vs 7 months, log-rank p<.03) but not with FL (17 vs 22 months). Although the median OS has not been reached in any of the histological group so far, no difference in its duration is detected between CCR- or COP-treated pts. In summary, for pts with SLL, MZL and FL, first-line CCR regimens provided better CR and similar toxicity rates as compared to COP, which translated into longer FFP in SLL and MZL but not in FL pts. Although these results warrant larger number of pts and longer follow-up, they might suggest the choice of different front-line chemotherapy with or without immunotherapy in particular histological subtypes of low-grade lymphoma.
A Phase 2 Study of Bortezomib in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL).
Authors: de Vos Sven , Fernando Donna , Schenkein David P. , Rosen Peter J. 
Published: October 2019

Abstract
The novel proteasome inhibitor bortezomib (Velcade®) is approved for the treatment of multiple myeloma following at least one prior therapy. Recently, bortezomib was shown to be active in relapsed mantle cell lymphoma and some low grade B-cell non-Hodgkin’s lymphomas. We conducted a phase 2 trial to evaluate the overall response rate (ORR) following treatment with single agent bortezomib in patients with relapsed DLBCL. Non-hospitalized patients with measurable disease, and a Karnofsky Performance Score > 60%, were eligible for the trial if they had relapsed after or were refractory to their most recent chemotherapy. Patients had to be either not eligible for high dose chemotherapy with stem cell support or had already received a stem cell transplantation. The treatment schedule was: bortezomib 1.3 mg/m2 via intravenous bolus on days 1, 4, 8, and 11 of a 21-day cycle for up to 8 cycles. Responses were assessed using the International Workshop criteria (J Clin Oncol. 1999;17:1244). Ten patients were enrolled in this trial with one screen failure. The mean age was 60 years (range 22 to 83). The study population was heavily pretreated with a mean of 4.6 (range 2 to 7) prior chemotherapy regimens. Three patients (33.3 %) had received high dose chemotherapy with stem cell transplantation. The mean number of treatment cycles received was 2.33 (range 1 to 8). One of nine patients had stable disease (SD) and completed all 8 treatment cycles whereas all other patients progressed while on study drug (PD). The treatment was well tolerated. Grade ≥ 3 AEs included thrombocytopenia, neutropenia, hyponatremia, and hyperkalemia. In summary, single agent bortezomib is not an active drug in heavily pretreated patients with relapsed/refractory DLBCL. Bortezomib has clinical activity as single agent in other lymphoma subtypes and there is at least additive preclinical and clinical activity in combination with other agents. Therefore, investigation of bortezomib-containing combination therapies might be considered in less heavily pretreated DLBCL patients.
Development of Dendritic Cell Vaccine Against Measles for Patients Following Hematopoietic Cell Transplantation.
Authors: Kumamoto Tadashi , Nashida Yuji , Hirayama Masahiro , Azuma Eiichi , Komada Yoshihiro 
Published: October 2019

Abstract
Measles virus (MV) remains one of the serious pathogens among patients following hematopoietic cell transplantation (HCT). According to our questionnaires reported in Japan Society for Pediatric Hematology from 170 institutes in 2001, 37 patients from 21 institutes were affected with measles after HCT and 3 out of these patients died. This high mortality rate is mainly due to secondary infection, which developed on the basis of immune suppression induced by MV infection. However, only 29 of 170 institutions performed measles vaccination after HCT. It is speculated that the potential of immune suppression by vaccine strain of MV is one of the major reasons for hesitating vaccination following HCT. MV-producing glycoproteins expressed in MV-infected cells play important roles in the induction of immune suppression. MV-infected DCs express measles glycoprotein complexes consisted of fusion (F) and hemagglutinin (HA) protein. During DC-T cell interaction, the signal transmitted from F-HA complex interferes with Jak/STAT and PI3-k/Akt kinase pathways, and eventually inhibits the survival and proliferation of T cells. Here, we produced a DC-based vaccine against MV by loading DCs with MV-infected autologous DCs. MV in the infected DC was inactivated using ultraviolet-B before loaded. The DC-based vaccine neither expressed HA nor inhibited allogeneic T cell proliferation, while induced the production of interferon (IFN)-gamma by autologous CD4+ and CD8+ naive T cells. Importantly, 19 out of 20 DC-vaccines effectively induced IFN-gamma producing cells in vitro, even when prepared from patients who suffered from acute or chronic GvHD, and were taking immunosuppressives. Surprisingly, IFN-gamma producing cells were induced in all 8 patients who had undergone HCT within a year (2 patients in 1 month, 2 in 2 months, 1 in 6 months, 2 in 7 months, and 1 in 10 months). These findings indicate that our DC-based MV vaccine induces MV-specific immunity even in post-HCT patients without immune suppression, and enable early immunization safely following HCT.
Delayed Hepatitis B Active Viral Replications without Active Viral Biochemical Hepatitis Two Months after Cessation of Pre-Emptive Adefovir Therapy in a Patient with Waldenstrom Macroglobulinemia Treated with Rituximab and Fludarabine Chemotherapy.
Authors: Hanbali Amr S. , Khaled Yasser 
Published: October 2019

Introduction:
Reactivation of HBV is a well-known complication in patients receiving cytotoxic therapy for malignancy. The incidence of hepatitis directly resulting from reactivation of HBV has been reported as 49% in HBs antigen-positive-patients with lymphoma. Preemptive use of lamivudine has successfully reduced the fatal complication of HBV reactivation after chemotherapy. The Optimal duration of Lamivudine adminstration has not yet been defined, although additional 1–2 months of therapy after chemotherapy cessation is recommended according to some studies.
The efficacy and duration of therapy with Adefovir has not been established in the same circumstances.
Method:
A 32-year-old Fillipino female, who presented in September 2004 with Waldenstrom Macroglobulinemia. She was found to have Hepatitis B surface antigen positive. Other Hepatitis B related laboratory testing revealed negative hepatitis B Delta antibody, negative hepatitis BE antigen negative hepatitis B core antibody IgM and positive hepatitis BE antibody.
Hepatitis B DNA less than 500 copies/ML. Patient was started on pre-emptive Adefovir during her treatment with 4 cycles of Fludrabine followed by four weekly treatment with rituximab. She achieved partial response and Adefovir was discontinued two months after completion of chemotherapy and Rituximab. Prior to proceeding with high dose chemotherapy with stem cell support four months after discontinuation of Adefovir, repeat hepatitis B DNA revealed more than 10 millon copies with normal biochemical profile.
Conclusion:
Use of adefovir for during and for 2 months after Rituximab containing chemotherapy was not successful in preventing reactivation of hepatitis B virus, and extreme caution should be practiced when treating a patient with a positive HBs antigen with Rituximab containing chemotherapy. Also the optimal duration for continuing HBV prophylaxis is not known, but clearly 2 months is a suboptimal duration. It is unknown if adefovir is as effective as lamivudine in preventing reactivation of HBV with Rituximab. The lag of HBV related hepatitis despite active viral replication cholud be related to prior immune-suppression by Rituximab and Fludarabine.
Accelerated Delivery of Rituximab Is Safe on an Out-Patient Basis.
Authors: Middleton Helen J. , Mollee Peter , Bird Robert , Mills Anthony K. , Marlton Paula , Gill Devinder 
Published: October 2019

Abstract
Aim
A prospective study to determine the safety of the accelerated delivery of rituximab.
Methods
A pilot study investigating the safety of the accelerated delivery of rituximab was commenced in September 2004. First doses of rituximab were delivered as per prescribing guidelines. Patients without infusion related toxicity were eligible for accelerated rituximab in second or subsequent infusions. In the first 4 patients the infusion was administered at 100mg/hr, increasing to 400mg/hr after 15 minutes in the absence of a reaction. All subsequent patients commenced the infusion at 400mg/hr. All patients received premedication with paracetamol, promethazine and hydrocortisone unless contra-indicated. Patients with a previous grade III/IV infusion related toxicity were excluded.
Results
23 patients have been enrolled to date. Data is available for 62 infusions - median 3 infusions per patient (range: 1–6). Median age was 64 years (range: 28–85). 65% of patients were male. Diagnoses included non-Hodgkin’s Lymphoma - 20 patients (Diffuse Large Cell Lymphoma - 8, Follicular Lymphoma - 9, Mantle Cell Lymphoma - 1, Lymphoplasmacytic Lymphoma - 2), Immune Thrombocytopenic Purpura - 2 and Dermatomyositis-1. 44% of patients received single agent rituximab and 56% received it in combination with chemotherapy. The median dose of rituximab was 700mg (range: 600–800mg). There were 2 adverse events with no grade III/IV infusion related toxicity. One patient experienced grade I hypothermia. A second patient experienced grade II fevers and rigors which required interruption of the infusion. The patient was subsequently found to have pneumonia. The infusion was completed without further incident. Excluding data from the latter patient, median infusion time was 1 hour and 55 minutes and 76% of infusions were completed within 2 hours.
Conclusion
For second or subsequent infusions, the accelerated delivery of rituximab is safe and well tolerated allowing shorter outpatient stays and improving the efficiency of resource utilisation. The study has been extended to include patients with bulky lymphoma and Chronic Lymphocytic Leukaemia.
CD30+ Lymphoproliferative Disorder/Lymphomatoid Papulosis - A Regression Caused by Mistletoe Therapy.
Authors: Seifert Georg , Tautz Christoph , Seeger Karl , Henze Guenter , Laengler Alfred 
Published: October 2019

Abstract
Lymphomatoid papulosis (LyP) is a CD30+ cutaneous lymphoma according to the WHO classifications and regarded as a condition of uncertain malignant potential. The incidence of LyP in children is relatively low compared to that in adults. It is correlated with malignant lymphomas in 5–20% of adult LyP-patients. In children, an increased risk for the development of a malignant lymphoma is observed. The clinical course is often chronic. Most common treatment for LyP is topical steroids, antibiotics, phototherapy and low-dose methotrexate. Prognosis is excellent with a survival of 100% even for patients with malignant lymphomas. Case-report: An 8-years old boy suffered from reddish nodules (maximum 7 cm in diameter) on his right forearm and his left leg. Immunohistochemical analysis identified a CD30+large-T-cell-type-NHL of the skin. Topic steroids were effective but six months later he showed axillar lymph-node swelling. Immunohistochemically it was classified as anaplastic large cell T-type-lymphoma (ALCL) without signs of systemic involvement. Combination chemotherapy according to the European ALCL-trial (high-risk-group) was given for six months. All nodules (cutaneous and lympoid/axilla) resolved within a few weeks. Two months after cessation of chemotherapy a new skin-nodule on the left forearm appeared. The immunohistochemical diagnosis was now LyP. No specific therapy was given. In the following two months he developed two further solid and painful skin-lesions. In this situation we decided to start a therapeutic approach with subcutaneous mistleote (MT), which was injected close to one of these lesions. The skin-nodules decreased after the first dose and MT injections into all nodules were continued. Within the following two weeks the skin-lesions resolved completely and subcutaneous MT therapy was continued. Two months later, he developed two new nodules responding within a few days to increased dose of MT. While continuation therapy with MT the boy was without clinical signs both of the LvP and ALCL for nearly two years. Subsequently MT therapy was terminated. Three weeks after cessation the cutaneus LyP generally reactivated all over the body with typical nodules (maximum 1 cm in diameter). Subcutaneus MT therapy was restarted and the cutnaneus LyP regressed within 2 weeks completely without additional therapy.