Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Chemotherapy Research Articles

A Retrospective Analysis: Autologous Peripheral Blood Hematopoietic Stem Cell Transplant Combined With Adoptive T-Cell Therapy for the Treatment of High-Grade B-Cell Lymphoma in Ten Dogs.

In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.

CHOP Plus Sequential Mogamulizumab As First-Line Therapy for Untreated Adult T-Cell Leukemia-Lymphoma

Introduction: Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. In younger patients, allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to improve prognosis through a graft-versus-ATL (GvATL) effect. On the other hand, elderly patients with ATL are often not amenable to HSCT, and the prognosis is extremely poor with existing chemotherapy. The most widely used chemotherapy for ATL, CHOP (combination of cyclophosphamide-doxorubicin-vincristine-prednisone) and similar chemotherapy, have shown a complete response (CR) rate of about 20% and a long-term prognosis of less than 10%. In a phase II study of mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, in concurrent combination with chemotherapy (mLSG15), the primary endpoint of CR was 52% in the mLSG15 + mogamulizumab group compared to 33% in the mLSG15 alone group. However, no improvement was observed in overall survival (OS) or progression-free survival (PFS). In addition, mLSG15 is a potent chemotherapy and not feasible in majority of elderly patients. Considering the possibility that mogamulizumab may unlock the tumor immune evasion mechanism by removing regulatory T cells and exert an immunological effect like GvATL, we investigated its usefulness as an immunological consolidation therapy following chemotherapy, with the aim of suppressing recurrence.Methods: New-onset treatment-naive ATL patients who were not eligible to HSCT received 3 courses of CHOP (combination of cyclophosphamide div 750 mg/m 2/day1, doxorubicin iv 50 mg/m 2/day1, vincristine iv 1.4 mg/m 2/day1 [max. 2.0 mg/body, and prednisone po/iv 100 mg/body/day1-5) at 21-day intervals, and then the first course of mogamulizumab (1 mg/kg for 8 doses at 2-week intervals) was initiated between the start of the third course of CHOP-21 and day 42. The primary endpoint was OS at months 12. Secondary endpoints were proportion of subjects with PFS, OS, overall response rate (ORR), organ-specific response rate, CR rate and adverse events (AEs) at month 12.Results: A total of 24 patients were enrolled and the median age was 75.5 years (range, 64-85). The median follow-up period was 11.0 (3.0-30.6) months. Five subjects discontinued study treatment before mogamulizumab administration attributable to insufficient effect (n=2), continuation deemed inappropriate (n=2), and start of the next course extended (n=1). ORR was 87.5%. Organ-specific response rates for peripheral blood, other than peripheral blood, target lesion, and skin lesion were 83.3%, 87.5%, 79.2%, and 66.7%, respectively.OS and PFS rates in the full analysis set (FAS) at months 12 were 52.6 (30.9-70.4)% and 26.6 (10.9-45.3)%, respectively. The median survival time (MST) and 80% confidence interval (CI) for OS was 12.1 (5.0 -21 .0) months (Figure 1). Since the lower limit of the 80% CI was below the threshold of 6 months, this treatment was not considered to be effective. However, the point estimate of MST was 12.1 months, which was equivalent to the expected value. One possible reason for the failure to reach statistical significance could be attributable to occurrence of events in the early stage of the protocol regimen. In other words, patients who did not respond to the preceding chemotherapy did not benefit from mogamulizumab, and only patients who managed to overcome chemotherapy benefited from the immune effects of mogamulizumab, resulting in long-term survival (Figure 1). In the long-term follow-up, the MST (95% CI) of the FAS was 12.4 (4.9-21.0) months, and the median OS (95% CI) at 24 months was 25.1 (9.6-44.1) %.AEs were observed in 16 subjects, of which serious AEs (grade 4/5) were observed in 5 subjects (acute respiratory distress syndrome, ventricular fibrillation, heart failure, hyponatremia, and pneumonia). Largely, AEs were resolved/recovered in 14 subjects including 3 subjects with serious AE; 2 subjects resulted in death, which were not considered treatment-related.Conclusions: Mogamulizumab as an immunological consolidation therapy after CHOP 21 might be one of the treatment options for transplant-ineligible elderly patients with previously-untreated ATL, despite not clearly showing improved OS. Further studies are warranted to examine the dosing timing of mogamulizumab to obtain its maximum benefit for prolonged survival. [Display omitted] DisclosuresKato: Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Dainippon-Sumitomo: Honoraria; Eisai: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; MSD: Honoraria; Mundi: Honoraria; Novartis: Consultancy, Research Funding; Ono: Honoraria, Research Funding. Suzuki: Kyowa-kirin: Honoraria, Research Funding, Speakers Bureau; Chugai: Honoraria, Research Funding, Speakers Bureau; Taiho: Research Funding; Ohtsuka: Honoraria, Research Funding; Takeda: Research Funding, Speakers Bureau; Shionogi: Research Funding; Eisai: Honoraria, Research Funding; Bristol-Meyer Squib: Honoraria; MSD: Honoraria; Janssen: Honoraria; Abbvie: Speakers Bureau; Meiji Seika: Honoraria, Speakers Bureau; Ohtsuka: Honoraria. Akashi: Sumitomo Dainippon Pharma: Consultancy; Kyowa Kirin: Consultancy, Research Funding; Celgene: Research Funding; Astellas Pharma: Research Funding; Shionogi: Research Funding; Asahi Kasei Pharma: Research Funding; Chugai: Research Funding; Bristol-Myers Squibb: Research Funding.

GM-CSF enhanced the effect of CHOP and R-CHOP on inhibiting diffuse large B-cell lymphoma progression via influencing the macrophage polarization

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a common type of the Non-Hodgkin lymphomas (NHLs) formed by the neoplastic transformation of mature B cells. As the first-line therapeutics, CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and R-CHOP (Rituximab + CHOP), either using alone or in combination with GM-CSF, have achieved great efficacy in DLBCL patients. However, the underlying mechanisms are still largely unknown.MethodsIn the present study, the combination use of CHOP and R-CHOP with GM-CSF was used to evaluate their effects on the tumor immune microenvironment of DLBCL. CHOP and R-CHOP administration was found to inhibit the growth and metastasis of DLBCL, with a higher efficacy in R-CHOP-challenged DLBCL mice. The anti-tumor effect of CHOP and R-CHOP was further amplified by GM-CSF.ResultsCHOP and R-CHOP therapeutics potentiated the anti-tumor properties of macrophages, as evidenced by the increased M1 macrophage and the decreased M2 macrophage accumulation in DLBCL-bearing mice. In a co-culture system, macrophages primed with CHOP and R-CHOP therapeutics inhibited multiple malignant behaviors of DLCBL cells. Mechanistically, CHOP/R-CHOP suppressed the activation of AKT signaling. These anti-tumor effects of CHOP/R-CHOP were all augmented by GM-CSF.ConclusionsOur work provided new insights into the immune-regulatory roles of CHOP and R-CHOP in the treatment of DLBCL, as well as the synergistic effects of GM-CSF in CHOP and R-CHOP therapeutics. Although our results suggest the synergistic effect of GM-CSF on DLBCL already sensitive to CHOP and R-CHOP, however, future studies are warranted to explore the role of GM-CSF on R-CHOP-resistant DLBCL.Trial registration Not applicable.

Exploring the burden of short-term CHOP chemotherapy adverse events in post-transplant lymphoproliferative disease: a comprehensive literature review in lymphoma patients

Purpose Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients. Design This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies. Results PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations. Conclusions Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.

Clinical features and outcome of the patients with sinonasal tract diffuse large B-cell lymphoma in the pre-rituximab and rituximab eras.

Sinonasal tract diffuse large B-cell lymphoma (SNT-DLBCL), a rare extranodal lymphoma, is not well characterized. We performed a population-based study to determine cell-of-origin, clinical presentation and impact of rituximab (R) and central nervous system (CNS) directed chemotherapy on survival. Patients with SNT-DLBCL were identified from pathology databases. Clinical information was collected and outcomes between different treatment modalities evaluated. Thirty-two percent of the patients had germinal centre B-cell phenotype. Forty-six patients were treated with curative intent using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like chemotherapy, 21 (46%) before and 25 (54%) in the R-era. Additionally, 24 (52%) received CNS-directed chemotherapy. Addition of R to chemotherapy reduced the risk of progression (RR=0.368, 95% CI 0.138-0.976, P=0.045) and death (RR=0.245, 95% CI 0.068-0.883, P=0.032), and translated into better survival (5-year PFS, 67% vs 38%, P=0.037; 5-year OS, 81% vs 48%, P=0.020). CNS-directed chemotherapy reduced the risk of progression (RR=0.404, 95% CI 0.159-1.029, P=0.057) and death (RR=0.298, 95% CI 0.093-0.950, P=0.041), and translated into favorable survival (5-year PFS, 67% vs 32%, P=0.050; 5-year OS 82% vs 43%, P=0.030). Patients with SNT-DLBCL benefit from rituximab and CNS-directed chemotherapy.

Abstract 33: Clinicopathologic, immunophenotypic, diagnostic, treatment characteristics of non-Hodgkin's lymphoma: Diffuse large B cell: Primary ovarian and with ovarian extensive involvement

Abstract 33: Clinicopathologic, immunophenotypic, diagnostic, treatment characteristics of non-Hodgkin's lymphoma: Diffuse large B cell: Primary ovarian and with ovarian extensive involvement

Extracavitary primary effusion lymphoma associated with hemophagocytic lymphohistiocytosis.

Extracavitary primary effusion lymphoma associated with hemophagocytic lymphohistiocytosis.

A Case of Hepatitis B Virus Reactivation in a HBsAg-Negative and Anti-HBs-Positive Patient with Diffuse Large B-Cell Lymphoma after Rituximab plus CHOP Chemotherapy

The reactivation of hepatitis B virus (HBV) is well known complication among lymphoma patient related with chemotherapy. Rituximab is monoclonal antibody that targets B-lymphocytes for treatment of lymphoma and it increases reactivation of HBV. Although most of reactivation occurs in HBV carrier, it can also rarely occur when hepatitis B surface antigen (HBsAg) is negative. Furthermore it is less frequently reported in lymphoma patient when HBV serology shows HBsAg is negative and anti-HBs is positive. We report a case of HBV reactivation following 6 cycle of rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for diffuse large B-cell lymphoma in HBsAg negative/anti-HBs positive 58-year-old male, with a review of the literature.

In Vitro and in Vivo oncolytic Activity of Lasota Strain of Newcastle Disease Virus on a Lymphoma B-Cell Line and a Canine Cutaneous T-Cell Lymphoma

Oncolytic viruses, either naturally or genetically modified, possess the ability to kill cancer cells. Newcastle Disease Virus (NDV), a type I avian paramyxovirus, has demonstrated a selective ability to kill cancer cells directly as well as through immunostimulation. NDV is able to infect more than 250 species of birds, particularly poultry and is considered a zoonosis, primarily causing conjunctivitis. Importantly, no infections have been reported in mammalian species nor is there evidence of human to human transmission. We use the LaSota strain which is lentogenic (less pathogenic). We seek to study the in vitro oncolytic (lympholytic) potential of NDV on healthy mononuclear and malignant lymphocytes and the in vivo oncolytic therapeutic potential in dogs with lymphoma.LaSota vaccine strain (LSV) was propagated in pathogen –free 9 day old chicken embrios. Viral titers were reported as mean infective dose. Healthy human and canine mononuclear cells as well as a human diffuse large B cell lymphoma cell line (DHL4 cell line) were exposed to medium alone, LSV at a multiplicity of infection (MOI) of 0.1, 10 and 100 or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. Apoptosis was assessed by flow cytometry using annexin V/FITC/IT. Cell counts were carried out at 48 and 72 hs. Data was analyzed by FlowJo 9 and Prisma 6 Softwares. Interestingly, cells at the highest MOI (100) had the same rate of apoptosis as those exposed to chemotherapy, both significantly higher than negative controls.The in vivo response and toxicity to intravenous and intratumoral inyection of LSV in a dog with naturally occurring aggressive, multicentric cutaneous T-cell lymphoma is reported. The patient had a 4 week history of paraplegia due to lymphomatous infiltration of the spinal canal and a 3 week history of rapid development of multiple elevated cutaneous lesions ranging from (from 0.5 by 0.5 cm to 15 cm in diameter and 2 cm in thickness). After informed consent, LSV was given in a single occasion with 1x106 mean (50%) infective dose in tissue culture (TCDI 50) in only one lesion, as well as intravenously with a TCDI 50 of 1x1012 in order to assess response of distant non-virally infiltrated lesions. At four weeks of follow up, no new lesions have appeared. All tumors are responding with complete flattening of the lesions and decrease in diamenter of all lesions. Spontaneous bleeding from the lesions was seen from days 4 through 7 after treatment. All laboratory work up is within normal limits except for indirect hiperbilirrubinemia (2x above normal) in the 4th week (Coombs results are pending). Consecutive samples for histology, electron microscopy and viral load are being evaluated. The patient has had an excellent performance status with no evident clinical toxicity and has begun to wag his tail and show slow movement of the posterior limbs with gain in sensitivity.We have demonstrated the specific in vitro, oncolytic/lympholytic activity of NCV (LaSota) on human lymphoma- derived cells with minimal tropism towards healthy cells. Response to treatment of the first patient (dog) is encouraging. Longer follow up as well as histologic evaluation and viral shedding are being evaluated. DisclosuresNo relevant conflicts of interest to declare.

An Aggressive Primary Orbital Natural Killer/T-Cell Lymphoma Case

Natural killer/T-cell lymphoma (NKTCL) and its presentation with extranodal orbital involvement as a single lesion are extremely rare. The aim of this article was to describe the presentation, diagnosis, and systemic treatment of a primary orbital NKTCL. A 67-year-old Caucasian woman presented with left exophthalmos, pain, periorbital swelling, and limited extrinsic ocular motility. Orbital cellulitis was suspected, but finally orbital biopsy was performed due to no response to initial antibiotic and anti-inflammatory standard treatment. The pathologic diagnosis was NKTCL. Systemic evaluations were negative. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was initiated, but after 2 cycles of treatment, tumoral progression was observed. SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) rescue chemotherapy was then administered. Lymphoma progression was inevitable. She died 10 months later. Although more nasal NKTCL cases have been described, the nonnasal primary orbital NKTCL is an uncommon neoplasm with high mortality rate, despite the recent use of more potent chemotherapy regimens.

Frequent Relapse and Irradiation Strategy in Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg-type

The 2008 WHO–EORTC classification for cutaneous lymphomas identifies 3 main subtypes of primary cuta-neous B-cell lymphoma, including primary cutaneous dif-fuse large B-cell lymphoma, leg-type (PCLBCL, LT) (1), which is predominantly found in elderly people and has clinical features of erythematous or violaceous multiple tumours, frequent relapses, and a poor prognosis (1–3). Currently, CHOP (cyclophosphamide, doxorubicin, vin-cristine, prednisone) or rituximab plus CHOP (R-CHOP) chemotherapy is considered as a standard first-line therapy for PCLBCL, LT (1, 2, 4). Radiation therapy is less effective than in other subtypes of PCLBCLs. In case the condition of the patient does not allow application of chemotherapy, local irradiation of all visible skin lesions can be adopted. There is, however, no report or criteria for the selection of radiation treat -ment fields: involved field irradiation or extended field irradiation. This case report provides important insights for discussing frequent relapse and irradiation strategy in PCLBCL, LT.CASE REPORT

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy As Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy As Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas

Establishment and characterization of therapy-resistant mantle cell lymphoma cell lines derived from diff erent tissue sites

Mantle cell lymphoma (MCL) is a rare but aggressive form of B cell non-Hodgkin lymphoma in which therapy resistance is common. New therapeutic options have extended survival in refractory MCL but have not provided durable remission. Tools are needed to assess the molecular and genetic changes associated with therapy resistance. Therefore, therapy-resistant MCL cell lines were established from the liver, kidney and lungs of human Granta 519-bearing NOD-SCID (non-obese diabetic-severe combined immunodeficiency) mice following treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy in combination with bortezomib. The cytomorphologies, immunophenotypes, growth patterns in semi-solid agar, cytogenetic profiles and gene expression differences between these cell lines were characterized to identify major changes associated with therapy resistance. Therapy-resistant cell lines exhibit more aggressive growth patterns and markedly different gene expression profiles compared to parental Granta 519 cells. Thus, these stable therapy-resistant cell lines are useful models to further study the molecular basis of drug resistance and to identify clinically relevant molecular targets in MCL.

Cutaneous Castleman disease

A 59-year-old Korean man was diagnosed in 1999 with multicentric plasma cell variant of Castleman disease (CD). He received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy in 2000 with partial response followed by thalidomide, and then rituximab treatment without success, and finally high dose steroids. He presented to our clinic in 2007 for a second opinion regarding biopsy-proven refractory cutaneous involvement by CD. He had no B symptoms at that point and his main concerns were related to his skin lesions. His baseline positron emission tomography (PET) scan showed increased uptake by multiple lymph nodes. The constitutional symptoms of CD result from secretion of interleukin-6 (IL-6) by the hyperplastic lymph nodes. As CD is an IL-6 driven condition, we used siltuximab, a chimeric human-murine anti-IL-6 antibody for this orphan disease. Following written informed consent, the patient was enrolled in a Phase I study and was treated with the investigational agent siltuximab (CNTO328), 12 mg/kg intravenously every 2 weeks. Prior to this treatment the patient had scattered hyperpigmented CD lesions (top left); partial response had occurred by 6 months (top right) and after 24 months of siltuximab he had achieved an almost complete response (bottom), which has been maintained for more than 4 years of treatment. He has had no side effects and continues to receive silutuximab. His latest PET scan showed no abnormal uptake.

Long‐term follow‐up of patients with HIV‐related diffuse large B‐cell lymphomas treated in a phase II study with rituximab and CHOP

Long‐term follow‐up of patients with <scp>HIV</scp>‐related diffuse large <scp>B</scp>‐cell lymphomas treated in a phase <scp>II</scp> study with rituximab and <scp>CHOP</scp>

The impact of high-dose chemotherapy, autologous stem cell transplant and conventional chemotherapy on quality of life of long-term survivors with follicular lymphoma

In this study we investigated the quality of life (QoL) of long-term survivors with follicular lymphoma (FL) after high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) using two standardized questionnaires. Altogether, 124 patients with FL were included in the study. A total of 63 patients received HDCT with ASCT, and this group was compared with 61 patients who were treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy and supplementary radiation. In addition, the QoL of the patients was compared to the QoL of healthy people on the basis of two studies about the general health status of the German population. When the QoLs of the HDCT group and the conventional therapy group were compared, there was a tendency for better QoL in the HDCT group, maybe due to a higher proportion of patients in complete remission (CR) or a longer follow-up period in the HDCT group (8.5 years vs. 4.5 years in the conventional therapy group). In both the HDCT group and the conventional therapy group, the results of the questionnaires showed a reduced QoL compared to the healthy population. In this study, there was a tendency for better QoL in the HDCT group compared to the conventional therapy group. However, the negative impact of both HDCT and conventional therapy on the QoL of patients with follicular lymphoma should not be underestimated and should lead to the development of less toxic therapy strategies.

Primary T-Cell Lymphoma of the Urinary Bladder Presenting with Haematuria and Hydroureteronephrosis

Primary bladder lymphoma, a rare form of non-Hodgkin's lymphoma that is confined to the urinary bladder, is usually of B-cell origin. This report describes an extremely rare case of primary T-cell lymphoma of the urinary bladder. A 45-year-old man presented with haematuria, dysuria and loin pain. Ultrasonography and computed tomography showed a thickened left bladder wall and left hydroureteronephrosis. A diagnosis of primary T-cell lymphoma of the urinary bladder was made on the basis of clinical, radiological and histological findings. The patient, following transurethral resection, was treated with four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy with a good response and remains in clinical remission 12 months after treatment.

Rituximab and CHOP Chemotherapy Plus GM-CSF for Previously Untreated Diffuse Large B-Cell Lymphoma in the Elderly: A Wisconsin Oncology Network Study

Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) may potentiate rituximab activity by upregulating CD20 expression and activating effector cells necessary for antibody-dependent cellular cytotoxicity. GM-CSF was combined with standard rituximab + CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy (R-CHOP) in the treatment of elderly patients with de novo diffuse large B-cell lymphoma (DLBCL). Thirty-eight patients over the age of 60 years with newly diagnosed DLBCL were treated with R-CHOP every 21 days for 6-8 cycles and GM-CSF 250 µg/m2 per day on days 3-10. Patients were evaluated for response after cycles 4, 6, and 8. The primary endpoint was the rate of complete response, and secondary endpoints were progression-free survival (PFS), event-free survival, and overall survival (OS). Thirty-eight patients were enrolled, with a median age of 72 years, and 29% of patients having high-risk disease (International Prognostic Index [IPI] score ≥ 4). A complete or unconfirmed complete response (CR) was achieved in 53% of patients. After a median follow-up of 51.1 months, the 3-year PFS and OS were 78% and 84%. Twenty-one percent of patients discontinued protocol treatment because of chemotherapy-related toxicity and 16% because of GM-CSF toxicity. Dose intensity for planned chemotherapy cycles was 81.1%. These data suggest that survival outcomes may be modestly improved when GM-CSF is combined with R-CHOP in the treatment of elderly DLBCL. GM-CSF had toxicity precluding planned administration in 16% of patients, which may limit usefulness of this agent. Further investigation of GM-CSF in combination with rituximab-containing chemotherapy is warranted.

The 51st Annual Meeting of the American Society of Hematology

Significantly improved survival outcomes have been demonstrated with the addition of rituximab to first-line CHOP (R-CHOP; cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy administered as a 21-day cycle (CHOP-21) in young and elderly patients with diffuse large B-cell lymphoma (DLBCL). 1 Feugier P Van Hoof A Sebban C et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005; 23: 4117-4126 Crossref PubMed Scopus (1244) Google Scholar , 2 Pfreundschuh M Trumper L Osterborg A et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomized controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006; 7: 379-391 Abstract Full Text Full Text PDF PubMed Scopus (1712) Google Scholar , 3 Habermann TM Weller EA Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006; 24: 3121-3127 Crossref PubMed Scopus (1148) Google Scholar Hence, R-CHOP-21 is considered the standard of care for patients with DLBCL. In an effort to improve on the CHOP-21 regimen, Pfreundschuh et al evaluated an intensified CHOP regimen administered every 2 weeks (CHOP-14) and demonstrated an improvement in 5-year event-free survival (EFS) and overall survival (OS) compared with the standard CHOP-21 chemotherapy in patients aged 60 years to 80 years with previously untreated DLBCL. 4 Pfreundschuh M Trumper L Kloess M et al. Twoweekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004; 104: 634-641 Crossref PubMed Scopus (633) Google Scholar Furthermore, the RICOVER-60 trial demonstrated that the addition of rituximab to 6 cycles of CHOP-14 provided a significant survival advantage compared with 6 cycles of CHOP-14 alone in elderly patients with DLBCL. 5 Pfreundschuh M Schubert J Ziepert M et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008; 9: 105-116 Abstract Full Text Full Text PDF PubMed Scopus (882) Google Scholar Until recently, results from prospective randomized trials directly comparing R-CHOP-21 and R-CHOP-14 regimens were not available. Cunningham et al conducted a prospective trial to compare the R-CHOP-14 and R-CHOP-21 regimens in newly diagnosed patients with DLBCL. 6 Cunningham D Smith P Mouncey P et al. A phase III trial comparing R-CHOP 14 and R-CHOP 21 for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2009; 27 (abstract 8506).: 435s Google Scholar Interim results from this trial demonstrated similar overall response rates (ORRs; 88% vs. 91%; P < .139) and complete responses (CRs)/unconfirmed CRs (CRu; 63% vs. 58%; P < .183) with both regimens. At a median follow-up of 17 months, a 2-year failure-free survival of 74% (95% CI, 71%-77%) and a 2-year OS of 81% (95% CI, 78%-84%) were achieved.

A Systematic Review of Economic Analyses Studying Rituximab in R-CHOP Therapy in Patients with Non-Hodgkin Lymphoma

Objectives: To explore the use of pharmacoeconomic principles through examination of economic evaluations pertaining to the combination of the monoclonal antibody rituximab with conventional CHOP (cyclophosphamide/doxorubicin/ vincristine/ prednisone) or CHOP-like chemotherapy regimens in patients with non-Hodgkin lymphoma. Methods: A literature search was conducted using Evidence-Based Medical Reviews (EBMR), International Pharmaceutical Abstracts (IPA), and Medline databases to identify all economic studies relating to rituximab in combination with CHOP or CHOP-like regimens. The systematic evaluation also utilized the Quality of Health Economic Studies instrument to assess the quality of each study that was included in the final review. Results: Initially, eight studies were retrieved which included the use of rituximab in non-Hodgkin lymphoma treatment. Of these, four studies were excluded as rituximab was used as a stand-alone treatment option. The remaining four studies involved conventional CHOP therapy versus the combination with rituximab (R-CHOP) in patients with non-Hodgkin lymphoma. One study employed a cost-effectiveness analysis while the remaining three studies used a cost-utility analysis and reported the outcomes in terms of quality-adjusted life years (QALYs). Conclusions: The cost-effectiveness evaluation illustrated the dominance of R-CHOP over CHOP-alone in terms of both lower costs and increased life years gained. The cost-utility of R-CHOP in terms of costs/QALYs were below the accepted threshold of 50,000 in international monetary units. Through examination of evaluation principles employed, it is found that valid results are highly dependent on the input data, assumptions, and sensitivity analyses. Clinical decisionmakers must take into account specific inclusions of costs relevant to their own practice setting.