Cyclophosphamide, Adriamycin, Vincristine, And Prednisolone Research Articles

Phase 2 Study of Abbreviated 3 Cycles of Rituximab Plus CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) Immunochemotherapy in Patients with Completely Excised Stage I or II CD20+ Diffuse Large B-Cell Lymphoma (CISL 12-09)

▪Introduction: Full cycles of R-CHOP chemotherapy or abbreviated chemotherapy followed by radiotherapy are recommended as standard of care for limited stage (LS) diffuse large B-cell lymphoma (DLBCL). There are occasions when lesions are completely excised during the diagnostic surgical resection. In addition, initial surgical resection of the involved area is often performed in the treatment of intestinal lymphomas with LS disease due to obstructive lesions or perforation risk. As to these patients without residual gross lesions, however, the number of cycles of chemotherapy has not so far been questioned and full cycles of chemotherapy are usually performed. Thus, we aimed to investigate the effectiveness of an abbreviated three courses of R-CHOP chemotherapy in patients with completely excised stage I or II CD20+ DLBCL.Methods: This is a multicenter, single arm, phase 2 study designed to evaluate efficacy and safety of 3 cycles of R-CHOP chemotherapy in low risk LS DLBCL. Key inclusion criteria were as follows: pathologically confirmed CD20 positive DLBCL, age >18 years, stage I or II, and complete resection with no residual lesion after surgical resection. Patients with B symptoms, bulky disease, primary breast, testicular or CNS lymphomas were excluded. R-CHOP chemotherapy started within 6 weeks from surgical resection and was repeated every 3 weeks for 3 cycles. Prophylactic G-CSF was not administered. Radiologic tumor assessment was performed at baseline, every 3 months until 2 years, then every 6 months until 5 years after completion of study treatment. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival and safety. (ClinicalTrials.gov: NCT01279902.)Results: Twenty-three patients were enrolled between Dec 2010 and May 2013. Of these, one was excluded because of ineligibility and the remaining 22 patients were included in the analysis. The median age at diagnosis was 57 years (range, 29-77 years). Fourteen patients had stage 1 disease and the other eight had stage 2. Preoperative LDH level was available in 11 patients and it was elevated in two of them. Thus, preoperative IPI scores could be calculated in those 11 patients; 0 in 8, 1 in one, and 2 in one patients, respectively. Postoperative IPI scores were 0 in 11, 1 in 10 and 2 in one patients. Primary sites included intestine (n=15), cervical lymph nodes (n=4), stomach (n=1), tonsil (n=1) and spleen (n=1). All the 22 patients completed 3 cycles of R-CHOP chemotherapy as planned. With a median follow-up of 39.5 months (95% CI, 29.9-47.1 months), only one patient showed disease progression and died with the estimated 2-year DFS and OS rates of 95.0%. It was the only one patient with IPI of 2 with elevated LDH and age>60 that showed disease progression at 12.7 months. He had a splenic mass and underwent splenectomy followed by 3 cycles of R-CHOP. He underwent one cycle of salvage R-ESHAP chemotherapy but died of rapid disease progression. No grade 3 or 4 non-hematologic toxicities were observed. Neutropenia was the most common grade 3 or 4 hematologic toxicity which was noted in 8 (36.4%) patients. Three patients experienced G3 febrile neutropenia.Conclusions: Three cycles of abbreviated R-CHOP chemoimmunotherapy is an effective and safe therapeutic approach for patients with localized and completely excised DLBCL especially in those with low-risk IPI. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Case of Disseminated Extranodal Interdigitating Dendritic Cell Sarcoma Arising from Parotid Gland

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare tumor derived from professional antigen presenting cell and primarily found in lymph nodes, with rarer case report about extranodal presentation of IDCS. A 71-yr-old man was admitted with progressively enlarging and painless mass in the right parotid area for 2 months. Computed tomography of the neck and chest revealed enhancing mass in right parotid gland, multiple lymphadenopathies around neck and mediastinum, and an osteolytic metastasis at thoracic spine. Morphological and immunohistochemical analysis of an excisional biopsy specimen from parotid mass were consistent with a diagnosis of IDCS. Palliative chemotherapy with 6 cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) regimen and 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) regimen plus radiotherapy on parotid mass failed in tumor reduction. We describe a rare case of disseminated extranodal IDCS arising from parotid gland.

VNCOP-B plus rituximab therapy in elderly patients with aggressive B-cell non-Hodgkin lymphoma: A multicenter experience

CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety. We report our clinical experience in 8 collaborative institutions to determine if the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin) combination therapy plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. Between September 2004 and December 2007, 23 previously untreated patients, median age 73 years, 50.0% classified as high-intermediate/high-risk on the standard International Prognostic Index (IPI) entered this trial. Complete remission rate was 90.5%, with a 100% overall response rate (RR) at the end of induction therapy; overall survival (OS) rate at 3 years was 76.4% (median follow-up 744 days), with an 82.6% 3-year progression-free survival (PFS) rate (median follow-up 744 days). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the patients despite prophylactic administration of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia in 30.0%, respectively. There was no treatment-related mortality (TRM). Rituximab not only combined with chemotherapy but also given sequentially improved survival. R-VNCOP-B could be another option for elderly patients who are not considered to tolerate in receiving R-CHOP.

Gemcitabine‐based combination chemotherapy as salvage treatment for refractory or relapsing aggressive non‐Hodgkin's lymphoma

Although CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) or more intensive chemotherapy regimens with or without rituximab can cure around 50% of advanced-stage aggressive non-Hodgkin's lymphoma (NHL), a substantial proportion of the patients develop refractory or relapsing diseases. However, high-dose chemotherapy followed by autologous stem cell transplantation usually rescues a limited number of patients. Historically, traditional chemotherapy regimens, including ESHAP (etoposide, methylprednisolone, high-dose Ara-C, and cisplatin), ICE (ifosfamide, carboplatin, and etoposide), DHAP (high-dose Ara-C, cisplatin, and dexamethasone), and EPOCH (etoposide, doxorubicin, vincristine, cyclophosphamide, and prednisone) are used for salvage treatment in refractory or relapsing NHL [1]; however, the use of these regimens is often limited by the relatively severe toxicities. For example, high-dose Ara-C-containing regimens (ESHAP and DHAP) have significant hematological, skin, conjunctival, and mucosal toxicities [2,3]. Accumulated cardiac toxicity would be a major problem of anthracycline-containing regimens (EPOCH) for patients after standard first-line CHOP-based regimens [4]. Previous studies using ICE for a salvage chemotherapy regimen usually enrolled transplant-eligible patients, and the hematological toxicity remained significant, although the aggressive prophylactic granulocyte colony stimulating factor (G-CSF) was used [5]. Therefore, a safe and effective salvage chemotherapy regimen is needed for the treatment of relapsing or refractory aggressive NHL, irrespective of the initial response to chemotherapy, patients' age, or patients' comorbidities.

Oncogene Associated cDNA Microarray Analysis Shows PRAME Gene Expression is a Marker for Response to Anthracycline Containing Chemotherapy in Patients with Diffuse Large B-cell Lymphoma

CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) therapy achieves a response in more than 60% patients with diffuse large B-cell lymphomas (DLBCLs). However, DLBCL shows a heterogeneous response to chemotherapy, and some patients are refractory to CHOP therapy. This difference in response to therapy is most likely due to differences in biological characteristics. We used cDNA microarray analysis to identify genes differentially expressed in anthracycline containing chemotherapy-resistant DLBCLs (7 patients) compared with anthracycline containing chemotherapy-sensitive DLBCLs (6 patients). Nine genes on the cDNA chip showed increased expression in anthracycline containing chemotherapy-resistant patients. We chose the preferentially expressed antigen of melanoma (PRAME) gene because it showed the highest expression in anthracycline containing chemotherapy-resistant DLBCLs on the cDNA chip, and it has been linked to prognosis of hematological malignancies. We also examined the relationship between PRAME gene expression and progression-free survival (PFS) in 45 patients with DLBCL. The progression-free survival of PRAME-positive patients (n=12) was significantly worse than that of PRAME-negative patients (n=33) (p=0.0373). Our results therefore indicate that PRAME expression in DLBCL correlates with response to anthracycline containing chemotherapy.

Posttransplant lymphoproliferative disease presenting as jejunal perforation

Sir, A forty-nine year-old male underwent live related renal transplantation thirteen years ago for end stage renal disease secondary to bilateral vesicoureteric reflux. He was on prednisolone 10 mg per day and azathioprine 125 mg per day for maintenance immunosuppression. He presented with pain in his abdomen and vomiting that had been prevalent since the past day. Evaluation was suggestive of hollow viscous perforation which was confirmed by computed tomography of the abdomen. As laparotomy revealed a perforation with growth in the jejunum, a jejunal segment resection was done followed by jejunojejunal anastamosis. Histopathological investigation revealed that the growth was a diffuse, large B cell lymphoma [Figure 1]. Immunohistochemistry confirmed it to be a B cell variant of diffuse large cell NonHodgkin's lymphoma of the small bowel. Viral serology showed significant Epstein barr virus (viral capsid antigen) IgM and Epstein barr virus (nuclear antigen) IgG levels being normal. The patient was maintained on CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) regimen by a medical oncologist. Figure 1 H and E, (10 × 10) jejunum showing diffuse large cell lymphomatous infiltration of all layers Renal transplant recipients carry a three to five fold higher risk of malignancy as compared to healthy people. Posttransplant lymphoproliferative disease (PTLD) is second only to skin cancers in contributing to 12% of posttransplant malignancies and its incidence increases with time.[1] The risk of developing PTLD is highest within the first year after the transplant, and the probability decreases thereafter.[2] The incidence increases with the age of the patient and the duration and cumulative dose of immunosuppressive therapy. It is associated with high morbidity and mortality. Cumulative doses and longer duration of systemic glucocorticoids and azathioprine increase the incidence of nonHodgkin's lymphoma (NHL).[3] The single most important risk factor for developing PTLD is EBV infection. This association is well established and 80–90% of PTLD cases are associated with primary EBV infection or reactivation of previously acquired EBV.[4] Most cases of PTLD occur as nodal diseases, but they can present with localized symptoms involving organs such as the gastrointestinal tract, lungs, skin, liver, central nervous system, and infiltrative lesions in the allograft. Extranodal involvement occurs in more than 50% of the cases. The gastrointestinal tract is predominantly involved with an increased propensity for ulceration and perforation.[5] In our patient, the points of interest were: a) presentation as perforation, b) the neoplastic growth resected turning out as a diffuse B cell variant of nonHodgkin's lymphoma with positive Epstein barr viral serology.

Alveolar Langerhans Cell Histiocytosis - A Case Report

ABSTRACT Langerhans cell histiocytosis is a rare disorder, usually occurring in children and young adults. A five year old male child presented with ulcers in lower left alveolar ridge with mobility of adjacent teeth of four months duration. After all relevant radiological and histopathological investigations final diagnosis of multicentric langerhans cell histiocytosis stage - II was made. The patient was put on chemotherapy with CHOP (Cyclophosphamide, Adriamycin, Vincristine and Prednisolone) regimen three weekly for eight courses. Now after six months of cessation of chemotherapy, the patient is in complete clinical remission.

A Pilot Study of Alemtuzumab Plus Combination Chemotherapy for Newly Diagnosed Patients with Peripheral T-Cell Lymphomas.

The results of combination chemotherapy for peripheral T cell lymphoma (PTCL) still showed poor, although alemtuzumab monotherapy has therapeutic activity in PTCL. We evaluated the safety and effectiveness of several combination chemotherapies with alemtuzumab for treating newly diagnosed PTCL including advanced stage cutaneous T-cell lymphoma. Nine patients with PTCL were included. The pathologic subtypes were as follows: cutaneous T cell lymphoma (CTCL) in 2 patients, peripheral T cell lymphoma unspecified (PTCLu) in 2 patients, extranodal NK/T cell lymphoma, nasal type in 3 patients, angioimmunoblastic T cell lymphoma (AITL) in 2 patient. Patients received a 30mg of alemtuzumab intravenously over about 8 hours on the first day of combination chemotherapy. The combination chemotherapy regimens included: CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) in 2 patients; EPOCH (etoposide, prednisolone, vincristine, cyclophosphamide and adriamycin) in 2 patients; IMVP16-PL (ifosfamide plus mesna, methotrexate, etoposide and prednisolone) in 5 patients. Complete remission was achieved in 2 patients, and partial remission was achieved in 5 patients, only one patient encountered treatment related mortality (septic shock). Nine patients received nineteen cycles of alemtuzumab plus combination chemotherapy. Alemtuzumab infusion related adverse events were reported in 10 of 19 cycles and were mainly mild to moderate in severity. The most common events were shivers and chills during the alemtuzumab infusion period, which occurred in 8 of 19 cycles. Six (32%) cycles had one or more episodes of new onset NCI-CTC grade 3 or 4 anemia. In addition, erythropoietin use was reported in 7 patients. All of the cycles had grade 3 or 4 neutropenia and 8 (42%) cycles had grade 3 or 4 thrombocytopenia. Grade 3 hyponatremia and grade 3 or 4 hypokalemia were observed in 1 and 4 cycles, respectively. Ten cycles (53%) with neutropenic fever occurred during the treatments. Six (32%) sepsis, 1 septic shock, 2 pneumonia, 2 fungal infection and 2 herpes zoster were observed. There was no cytomegalovirus reactivation during the treatment. Although alemtuzumab plus combination chemotherapy had significant hematologic and infection complications, we concluded that alemtuzumab plus combination chemotherapy was well tolerated and could be recommended for treating newly diagnosed PTCL. However, evaluation in more patients with long-term follow up is warranted.Patients characteristicsSexAgeStageRegimenCyclesAdditional TxResponseCTCL1Female22IVAAlemtuaumab+EPOCH3RTx4 + 2 IMVP16-PLPartial remissionCTCL2Female48IIIAAlemtuaumab+IMVP16-PL2RTx4Partial remissionPTCLuFemale70IIIAAlemtuaumab+CHOP33 CHOPComplete remissionPTCLuFemale50IVBAlemtuaumab+IMVP16-PL1NoPartial remissionNK/T3Male51IVBAlemtuaumab+IMVP16-PL1NoPartial remissionNK/T3Male46IIEAAlemtuaumab+IMVP16-PL3RTx4 + 1 IMVP16-PLComplete remissionNK/T3Male74IIEAAlemtuaumab+CHOP2NoTRM5(Sepsis)AITLFemale75IIIBAlemtuaumab+EPOCH2NoProgressionAITLMale70IVBAlemtuaumab+IMVP16-PL2NoPartial remission1Subcutaneous panniculitis T cell lymphom2Cutaneous gamma-delta T cell lymphoma3Extranodal T/NK cell lymphoma, nasal type4Radiotherapy5Treatment related mortality

Angiotropic B‐Cell Lymphoma with Telangiectasia, Accompanied by Panniculitic Formation

A 67-year-old female presented with diffuse edema, generalized telangiectasia, and indurated skin plaques. Histopathological findings of the skin lesion included CD45+/CD79+/CD20+ large lymphoma cells that filled the vascular lumina and infiltrated the subcutaneous tissues with panniculitic formations. Three cycles of a CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) chemotherapy regimen resolved the skin manifestations. After five cycles of CHOP, however, she developed dementia-like symptoms. Three cycles of additional intrathecal chemotherapy (methotrexate, cytarabine and prednisolone) did not improve the neurological symptoms.

Primary central nervous system lymphoma: the clinical features and treatment of 22 cases.

To clarify the efficacy of chemotherapy after radiation therapy in immunocompetent patients with primary central nervous system lymphoma (PCNSL). A retrospective analysis of 22 PCNSL patients was performed. Twenty-two patients were divided into a combined treatment (chemotherapy after radiation) group and a radiation group. The survival curves, calculated according to the Kaplan and Meier method, were compared using the Log-rank and Wilcoxon statistical analyses. Eight patients were treated with radiation therapy alone, and their median survival time (MST) after diagnosis was 21.9 months. Fourteen patients were treated with chemotherapy after radiotherapy. Six patients received chemotherapy consisting of cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP), while 6 patients received carboplatin-based chemotherapy and 2 patients received methotrexate-based chemotherapy. The MST of these 14 patients was 34.4 months, which was not significantly better than that of the radiation therapy group (p=0.159). Leukoencephalopathy occurred in 3 patients, who received whole brain radiation. The use of chemotherapy after radiation has up to now been thought to be a standard treatment modality but CHOP or carboplatin-based chemotherapy did not improve the survival time.

Primary cerebral lymphoma: an argument for the use of adjunctive systemic chemotherapy.

Eleven patients with primary cerebral lymphoma were treated at a single institution over a 5 year period. Patient characteristics were typical of this rare disease. One patient died prior to receiving treatment and of the remaining 10, all received cranial irradiation and in addition, five received systemic cyclophosphamide, adriamycin, vincristine and prednisolone (CHOP) chemotherapy. Of the six patients who are alive and disease-free, five received the combined modality therapy. The median survival for those patients receiving cranial irradiation alone was 18 months and for the combined modalities was 25+ months. Combination systemic chemotherapy, in addition to cerebral irradiation, may convey a survival benefit in patients with primary cerebral lymphoma but this requires further investigation with multicentre, prospective randomized trials.