Rituximab plus liposomal pegylated doxorubicin in the treatment of primary cutaneous B-cell lymphomas.

BACKGROUND: In primary cutaneous B-cell lymphomas (PCBCL), radiotherapy - or surgery in a minority of cases - is the first-line treatment in follicle center lymphoma (PCFCL) and marginal zone B-cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B-cell lymphoma, leg type (PCLBCL-LT), due its poorer outcome, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach. AIMS: Based on the favorable results reported with R and PLD in several recent trials, we decided to test efficacy and safety of this combination. METHODS: Twelve patients with PCBCL were treated with R plus PLD, and 7 had relapsed disease. Treatment plan consisted of 2 monthly cycles of R 375 mg/m(2) and PLD 20 mg/m(2) day 1;15, followed (in responders) by two cycles given only at day 1. All patients received prophylactic pyridoxine to prevent palmar-plantar erythrodysesthesia (PPE). RESULTS: Ten of 12 patients had a response (eight complete; two partial), remarkably 2/3 with PCLBCL-LT. Two patients did not respond (one progressive disease, PD, and one stable disease). Three patients died after a median follow-up of 56 months, two patients due to PD, and 1 due to a second neoplasm. Two out of 10 responders relapsed after 31 and 32 months, respectively. Hematological toxicity was negligible (one case of grade 2 neutropenia), as well as extra-hematological toxicity (two cases of grade 2 PPE). CONCLUSIONS: These preliminary data suggest that R-PLD is effective and well tolerated in all subsets of PCBCL and may be offered frontline in indolent cases unsuitable for radiotherapy or surgery as well as in more aggressive cases with contraindications to CHOP-like regimens.

Evidence for reduced angiogenesis in bone marrow in SSc: immunohistochemistry and multiparametric computerized imaging analysis.

OBJECTIVE: Dysfunctional angiogenesis is a pathogenetic marker of SSc. Circulating levels of endothelial progenitor cells are reduced, and mesenchymal stromal cells show a reduced differentiation into endothelial cells and capacity to form capillaries. This suggests that pathophysiologically relevant changes may already exist in SSc bone marrow (BM) stromal cells that may affect downstream angiogenesis. The aim of this study is to evaluate, in SSc BM, angiogenesis, cellular immune system and fibrosis. METHODS: Eight SSc patients affected by a severe dcSSc and screened for autologous haematopoietic stem cells transplantation (HSCT) underwent a BM biopsy. BM biopsies were compared with six healthy controls. To evaluate angiogenesis and cellular immunity, the following antibodies were used: vascular endothelial growth factor (VEGF), kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/flk-1), MMP-9 and CD34. To evaluate fibrosis, silver impregnation for reticulum was used. The number of vessels, the mean area of vascularization, the perimeter and microvessel density (MVD) were measured with a multiparametric computerized imaging analysis. RESULTS: A significant reduction in BM vascularity was found, while VEGF expression was much higher in SSc BM samples. Two patients had a Grade 2, whereas another two had a Grade 1 fibrosis. CONCLUSION: In SSc, BM is characterized by a reduction of microvascular density and number of vessels and a significant increase of VEGF. This indicates that BM may be involved in the process of loss of angiogenesis, despite the presence of high local and systemic levels of VEGF.

Drug-specific Th2 cells and IgE antibodies in a patient with anaphylaxis to rituximab.

Rituximab (RTX) is currently used in the treatment of lymphoproliferative diseases and of several rheumatologic disorders and is a frequent cause of acute infusion reactions, usually classified as cytokine release syndrome (CRS). Some infusion reactions to RTX raise concern for immediate type I hypersensitivity, even if to date RTX-specific IgE antibodies have not been reported. To improve knowledge of the mechanisms of reactions to RTX, we investigated humoral and cellular immune responses to this drug in a patient suffering from rheumatoid arthritis who displayed two immediate infusion-related reactions. RTX-exposed tolerant patients and healthy untreated subjects were used as controls. Non-isotype-specific and IgE anti-RTX antibodies were positive in the serum samples collected from the reactive patient but not in those from the control groups. Only the reactive patient also displayed skin testing positivity with RTX. More importantly, RTX-stimulated peripheral blood mononuclear cells from the reactive patient, but not from the controls, displayed a dose-dependent proliferative response associated with a Th2 cytokine production profile. Our results show the presence of RTX-specific Th2-type cells and IgE antibodies, thus suggesting that type I hypersensitivity may be an additional mechanism to CRS in the development of RTX reactions.

Underestimated Needs for Lymphoma Patients: An Assessment Issue.

BACKGROUND AND AIM OF THE WORK: The aim of the current study was to explore under-considered psychosocial needs for lymphoma cancer group. A model of the role of psychosocial factors and Stressful Life Events was operationalized. METHOD: We used Discriminant Analysis to test predictive power of the model. 103 oncological patients (gender: 42.7 % vs 49.3 % of females 55.2 ±15.6 vs 53.7±14.9) were matched with 140healthy control groups in the study. The following instruments were utilized to conduct the study: the Florence Psychiatric Interview, Hospital Anxiety Depression Scale, Multidimensional Scale of Perceived Social Support, Beck Depression Inventory I, and Sense of Mastery. RESULTS: The model satisfied the assumption criteria and were significant (Ʌ= .665, χ2= 105.83, p< .001). CONCLUSION: Stressful events, depression and anxiety were adequate markers of the psychological status of lymphoma patients. Our results point out the relevance of taking into account psychosocial factors in hematology.

Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia.

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.

Efficacy and safety of pegylated liposomal doxorubicin in primary cutaneous B-cell lymphomas and comparison with the commonly used therapies.

OBJECTIVES: The therapy of advanced, relapsed or refractory primary cutaneous lymphomas is often unsatisfactory. Recent data indicate a favourable pharmacokynetic, pharmacodynamic and toxicity profile of pegylated liposomal doxorubicin (Peg-Doxo) in primary cutaneous T-cell lymphomas, while in primary cutaneous B-cell lymphomas (PCBCLs), the drug efficacy has never been assessed so far. METHODS: We performed a prospective phase II pilot clinical trial of Peg-Doxo monotherapy (20 mg/m(2)) in PCBCLs. One patient had a marginal zone B-cell lymphoma and four were affected by diffuse large B-cell lymphoma-leg type, all with widespread nodular lesions. RESULTS: All the patients achieved a complete response (CR = 100%) in a short period of time (median 3 months), even when pretreated with radio-chemotherapy. Two experienced a relapse. At follow-up, one patient died for progressive disease; four are in CR after 5, 52, 63 and 69 months. As concerning the toxicity profile, the treatment was well-tolerated, no one decreased or delayed the dose. The haematological toxicity was mild with only one case of grade III neutropenia; a patient showed a grade I neurotoxicity. Dermatological toxicity, in particular the palmar-plantar erythrodysesthesia, did not occurred, probably because of both the low dosages of Peg-Doxo monotherapy and the oral prophylaxis with pyridoxine. CONCLUSIONS: In spite of the small number of patients, it emerges that monochemotherapy with Peg-Doxo has a significantly high clinical activity and a good safety profile in PCBCLs, even in aggressive forms, compared with other therapeutic regimens, which are completely reviewed. It suggests the need of further investigations in this field.

Multispectral imaging autofluorescence microscopy in colonic and gastric cancer metastatic lymph nodes.

BACKGROUND & AIMS: The lymphadenectomy and extended lymphadenectomy procedures have been points of controversy in surgical oncology. The methods available for the detection of metastatic lymph nodes are numerous. These include lymphoscintigraphy and radiolabeled antibody detection, but in most cancers the currently used technique is sentinel lymph node identification, performed primarily through the use of immunohistochemistry. We propose the application of autofluorescence (AF)-based techniques for lymph node evaluation in colorectal and gastric tumors. METHODS: We studied 30 clinical cases: 15 colorectal cancers and 15 gastric cancers. All of the patients were in the advanced stages of the disease and were candidates for adjuvant therapy. Autofluorescence microspectroscopy and multispectral imaging autofluorescence microscopy have been used to analyze the AF emission of metastatic lymph node sections, excited with 365-nm wavelength radiation. The AF spectra were recorded in the range of 400-700 nm. Monochrome AF images were acquired sequentially through interference filters peaked at 450, 550, and 650 nm, and then combined together in a single red-green-blue image. The AF pattern and the emission spectrum of metastatic lymph nodes have unique characteristics that can be used to distinguish them from the normal ones. RESULTS: The results, compared with standard histopathologic procedures and with specific staining methods, supplied a satisfactory validation of the proposed technique, revealing the possibility of improving the actual diagnostic procedures for malignant lymph node alterations. CONCLUSIONS: With the development of appropriate instrumentation, the proposed technique could be particularly suitable in intrasurgical diagnosis of metastatic lymph nodes.

Pegylated liposomal doxorubicin in the treatment of primary cutaneous T-cell lymphomas.

Pegylated liposomal doxorubicin (Peg-Doxo) is a promising drug for advanced/recalcitrant primary cutaneous T-cell lymphomas (CTCLs). This prospective phase II trial enrolled 19 patients. We observed overall and complete response rates of 84.2% and 42.1% (with no significant differences between stage I-IIA and IIB-IV patients), and 11% grade III/IV toxicity. After a maximum 46 month-follow-up, median overall (OS), event-free (EFS) and progression-free (PFS) survival were 34, 18 and 19 months. OS, EFS and PFS rates at 46 months were 44%, 30% and 37% respectively. Peg-Doxo seems to be an active and safe principle that should be used in plurirelapsed, early stage-MF and in combination with other chemotherapeutic agents in advanced and aggressive CTCLs.

Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides.

INTRODUCTION: Bexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes. We aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS. METHODS: We followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. "Mini" and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS). RESULTS: After induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades. CONCLUSIONS: We observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.

18FDG-positron emission tomography in post treatment evaluation of residual mass in Hodgkin's lymphoma: long-term results.

In patients with Hodgkin's lymphoma (HL) at the end of first line therapy an accurate imaging technique with high prognostic value is needed to assess response to treatment and predict those patients who will suffer disease relapse. This technique and its results permit the quick initiation of a second line therapy in patients suffering from a progressive disease or those unresponsive to treatment avoid over-treatment of patients in complete remission or those having a non-active residual disease. We included a (18)FDG-positron emission tomography (PET) scan to the diagnostic set-up to investigate 28 patients following the end of their treatment. Fifteen patients out of the 28 (54%) had positive CT scans while 13 (46%) had negative ones. Eleven patients out of the 15 CT positive (73%) had negative PET scans and no relapse. The remaining four patients (27%) had positive PET scans with only one relapse (25%). With respect to the 13 patients who had negative CT scans, 9 patients (69%) had negative PET scans and no relapse. The remaining 4 patients (31%) had positive PET scans with 3 relapse cases (75%). In our final assessment after a median follow-up period of 45 months, starting from PET execution to the last follow-up, overall sensitivity of the CT and the PET were 25 and 100% respectively, specificity 42 and 83% respectively, positive predictive value (PPV) 7 and 50% respectively, negative predictive value (NPV) 77 and 100% respectively, and accuracy 39 and 86% respectively. In our experience, FDG-PET performed in patients after induction therapy appears to offer important additional information: FDG-PET results are predictors of prognosis giving 100% DFS in PET negative patients and 54% DSF in PET positive patients.

The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases.

In order to elucidate the role of anthracycline based combination chemotherapy regimens for the treatment of follicular lymphoma we conducted a retrospective study on a large series of patients with a histologically confirmed diagnosis of follicular lymphoma. The Italian lymphoma intergroup (ILI) promoted a retrospective study of patients with follicular lymphoma treated in cooperative trials between 1985 and 1996. Six hundred and thirty three cases were treated with an anthracycline-containing regimen and 128 patients were treated without anthracyclines. The two groups were prognostically comparable; in particular, no difference was observed according to both IPI and ILI prognostic index. Results showed a complete remission (CR) rate for patients treated with anthracyclines was 69.2% and overall response rate was 92.5%. After a median follow-up of 51 months (54 months for patients still alive), the 5- and 10-year overall survival (OS) rates were 80 and 66%, respectively. Disease-free survival (DFS) and failure-free survival (FFS) rates at 5 years were 61 and 49%, respectively. In the group of patients treated with combination chemotherapy not including anthracyclines, the CR rate was 67.5% and the overall response rate was 85.4%. A longer OS (80% at 5 years) was observed in patients treated with anthracyclines compared to 67% OS rate in patients treated without anthracyclines (p = 0.0004). FFS was significantly longer in patients treated with anthracyclines (49 vs. 34% p = 0.006). Patients treated with anthracyclines with low or intermediate risk according to ILI prognostic index showed a significantly longer OS (p = 0.0001 andp = 0.0009, respectively); those in the high-risk group showed a trend for a longer survival. In conclusion, this retrospective study shows that patients with follicular lymphoma treated with an anthracycline containing regimen had a better outcome compared to patients treated with other combination regimens non including anthracyclines in terms of CRs, OS and FFS. On the basis of these results anthracycline-containing regimens (ACR) should be considered as the standard treatment of patients with advanced follicular lymphoma.

Immunohistochemistry analysis of bone marrow biopsies in multiple sclerosis patients undergoing autologous haematopoietic stem cells transplantation.

OBJECTIVE: Recently autologous haematopoietic stem cell transplantation (AHSCT) has been introduced for the treatment of severe forms of multiple sclerosis (MS). As little data are available on bone marrow (BM) of MS patients undergoing AHSCT, we investigated the morphological and phenotypic characteristics of MS BM. METHODS: BM biopsies of 14 MS patients screened for AHSCT and 10 control patients were evaluated to assess cellularity, morphology, immunological profile and bone marrow microenvironment. Immunohistochemistry analysis was performed to evaluate the expression of CD3, CD4, CD8, CD20, CD68, CD45, MMP-9. RESULTS: 8 out of 14 MS (57%) patients showed a reduction of age-related bone marrow cellularity, possibly due to previous immunosuppressive therapies. There were no differences in the T CD3+ lymphocyte expression rate amongst MS and the control patients, the CD4/CD8 ratio (2:1) was maintained as was the rate of B lymphocytes. We found an increased, although not significant, MMP-9 expression (9.2%) in the bone marrow of MS patients, when compared to the control patients (6.3%). CONCLUSION: The BM of MS patients showed a reduced cellularity and CD45+ cells content in comparison to the controls. A slightly increased expression of MMP-9 was also shown, possibly confirming an involvement of this compartment in the pathogenesis of the disease.

Patients with ≥ 20 × 10(9)/l platelets at baseline may have a prompt response to romiplostim during the early phase of treatment: an italian single-institution experience.

Patients with chronic immune thrombocytopenia treated with romiplostim may benefit from a higher starting dose when a rapid increase in count is needed, but it could be avoided in those with a prompt response to the standard dosage. We hypothesized that a platelet count ≥ 20 × 10(9)/l at baseline could distinguish subjects with such response from those with a delayed one during the early phase of treatment. Our work is a retrospective and single-institution analysis comparing the median platelet count, the median weekly dosage of romiplostim and the median number of weekly platelet counts < 50 × 10(9)/l between patients with a baseline ≥ 20 × 10(9)/l platelets (n=10, 2 splenectomized) and those with a lower one (n=8, 3 splenectomized) during the first month of treatment with romiplostim. The results show a higher median platelet count (79,5 vs 40,5 × 10(9)/l, p=0,002) and a lower median dose of romiplostim (1 vs 2 mcg/kg/week, p=0,01) in subjects with a baseline ≥ 20 × 10(9)/l platelets, who also had a trend of less weekly counts < 50 × 10(9)/l platelets (1 vs 2, p=0,054). These data suggest that patients with ≥ 20 × 10(9)/l platelets at baseline may achieve a prompt response with the standard dose of romiplostim, but further and larger data are needed in order to assess whether it can be considered in clinical practice.

Single dose palonosetron and dexamethasone in preventing nausea and vomiting induced by high emetogenic ABVD regimen in Hodgkin Lymphoma patients.

To evaluate the efficacy of a new agent, palonosetron, in Hodgkin Lymphoma patients treated with ABVD regimen. Complete response during the overall phase of the first ABVD cycle, was the primary endpoint. Secondary end points were: emesis-free patients and use of rescue medication during the acute and overall phases. From January 2008 to February 2009 36 patients were enrolled. The primary endpoint (CR 0-120 h) was achieved by 55.6% patients. In conclusion our study demonstrated that a single dose of palonosetron plus a single dose of dexamethasone was effective in preventing CINV in patients treated with ABVD regimen.

Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines.

BACKGROUND: To assess the efficacy and safety of the combination of non-pegylated liposome-encapsulated doxorubicin (Myocet(R)) with cyclophosphamide, vincristine, prednisone and rituximab (R-COMP) in patients with aggressive non-Hodgkin's B-cell lymphomas. METHODS: Twenty-one patients were selected for the presence of negative concurrent clinical features such as cardiac comorbidity and/or previous treatment with anthracycline-based regimens. Liposome-encapsulated doxorubicin at a dose of 50 mg/m(2) was administered in association with cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), prednisone (40 mg/m(2)) and rituximab (375 mg/m(2)) every 21 days for four to six cycles unless progression or unacceptable toxicity occurred. RESULTS: A complete response (CR) was obtained in 16/21 patients (76%), three patients achieved a partial response (14%), with an overall response rate of 90%. Two patients (10%) did not respond to therapy. After a median follow-up of 13 months (range 2-36 months), 2/16 CR patients relapsed, with a disease-free survival (DFS) of 78%. CONCLUSIONS: The replacement of doxorubicin with its non-pegylated liposomal pharmaceutical analogue was well tolerated and highly effective in inducing remission in this group of patients at high risk for cardiac toxicity or previously treated with anthracyclines. Its high tolerability and low incidence of cardiac events (only one patient) warrants further studies to confirm the clinical benefits of liposomal doxorubicin in this subset of patients.

Rituximab and chlorambucil as first-line treatment for low-grade ocular adnexal lymphomas.

Ocular adnexal lymphomas (OALs) are typically low-grade lymphomas and are largely represented by marginal-zone lymphomas (EMZL). Radiotherapy is the treatment of choice but is frequently associated to local complications. We investigated the association of chlorambucil and rituximab as first-line treatment for primary OALs. Nine consecutive, newly diagnosed OALs patients (eight with a EMZL, one with a follicular lymphoma) with a median age of 78 years were treated with this combination. Eight patients were in stage I-A, and one was in stage IV-A; all patients had low LDH values. Eight patients (89%) obtained a complete remission and one a partial response. All completed the treatment without significant toxicities. After a median follow up of 25 months, all patients are alive; no progressions or late toxicities were observed. Rituximab in combination with chlorambucil proved to be a feasible option as first-line treatment for OALs because of its feasibility and the absence of toxicity and local sequelae.

Dose-dense CHOP plus rituximab (R-CHOP14) for the treatment of elderly patients with high-risk diffuse large B cell lymphoma: a pilot study.

BACKGROUND: Aggressive non-Hodgkin's lymphomas (NHL) require intensive therapies which seemed impracticable in elderly patients. Dose reduction and therapy attenuation reduced treatment-related toxicity, but also decreased therapeutic efficacy. In elderly patients too, the achievement of complete remission is the most important prognostic factor affecting outcome. Therefore, we have treated elderly patients with a dose-intensified protocol. Aim of the study was to verify the feasibility of this scheme in a subset of patients with high-risk aggressive lymphomas. METHODS: Between June 2002 and June 2004, 26 patients over the age of 60 years with a diagnosis of aggressive NHL and an intermediate-high or high International Prognostic Index were treated with biweekly CHOP plus rituximab with the support of granulocyte colony-stimulating factors (G-CSF). RESULTS: Seventeen patients (65%) regularly kept the interval between cycles. Haematological and extrahaematological toxicities were moderate in all the patients. Twenty (77%) patients achieved complete remissions, 6 (23%) partial remissions with an overall response rate of 100%. After a median follow-up of 23 months, the overall survival was 79%; after a median follow-up of 17 months, the disease-free survival was 70%. CONCLUSION: These results confirm that a dose-dense CHOP programme can be administered safely and effectively in a subset of elderly patients with high-risk aggressive NHL. The addition of rituximab could increase the response rate without adding toxicity.

Prognostic factors in primary cutaneous B-cell lymphoma: the Italian Study Group for Cutaneous Lymphomas.

PURPOSE: Primary cutaneous B-cell lymphomas (PCBCLs) are a distinct group of primary cutaneous lymphomas with few and conflicting data on their prognostic factors. PATIENTS AND METHODS: The study group included 467 patients with PCBCL who were referred, treated, and observed in 11 Italian centers (the Italian Study Group for Cutaneous Lymphomas) during a 24-year period (1980 to 2003). All of the patients were reclassified according to the WHO-European Organisation for Research and Treatment of Cancer (EORTC) classification. RESULTS: Follicle center lymphoma (FCL) accounted for 56.7% of occurrences, followed by marginal-zone B-cell lymphoma (MZL; 31.4%); diffuse large B-cell lymphoma (DLBCL), leg type, was reported in 10.9% of patients. Radiotherapy was the first-line treatment in 52.5% of patients and chemotherapy was the first-line treatment in 24.8% of patients. The complete response rate was 91.9% and the relapse rate was 46.7%. The 5- and 10-year overall survival (OS) rates were 94% and 85%, respectively. Compared with FCL/MZL, DLBCL, leg type, was characterized by statistically significant lower complete response rates, higher incidence of multiple cutaneous relapses and extracutaneous spreading, shorter time to progression, and shorter OS rates. The only variable with independent prognostic significance on the OS was the clinicopathologic diagnosis according to the WHO-EORTC classification (DLBCL, leg-type, showed a significantly worse prognosis v FCL and MZL; P < .001), whereas the only variable with independent prognostic significance on disease-free survival was the presence of a single cutaneous lesion (P = .001). CONCLUSION: Our study identifies a possible PCBCL subclassification and the extent of cutaneous involvement as the two most relevant prognostic factors in PCBCL. These data can be considered reasonably as the clinical background for an appropriate management strategy.

Combined chemotherapy with carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor for the treatment of aggressive non-Hodgkin lymphoma: a long-term follow-up study.

BACKGROUND: The standard treatment for patients with aggressive non-Hodgkin lymphoma (NHL) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Since 1989, the authors have used a new chemotherapy regimen with combined carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor called BAVEC-MiMA. The objective of the current study was to explore, after a long follow-up period, the impact of this third-generation regimen for the treatment of aggressive NHL. METHODS: One hundred and one consecutive patients (median age, 41 years) with either B-cell (n=94 patients) or non-B-cell (n=7 patients), aggressive lymphoma were diagnosed and treated between 1989 and 1999 with the BAVEC-MiMA regimen. RESULTS: The complete response rate was 74%, and the overall response rate was 89%. Eleven patients with refractory disease died rapidly after a median period of 5 months. The major toxicity was Grade 4 neutropenia (according to World Health Organization criteria), which was observed in 15 patients (15%). There were four toxicity-related deaths. The overall survival rate was 63% at 9 years. In multivariate analysis, factors that were associated with advantage in overall survival were response to induction therapy, bulky disease, and high score on the International Prognostic Index (IPI). The disease-free survival rate was 77% at 9 years. In multivariate analysis, the IPI was the most important variable for the definition of disease-free survival. CONCLUSIONS: The BAVEC-MiMA regimen was feasible on an outpatient basis, it was tolerated well, and it showed a low toxicity-related mortality. The long follow-up in patients with NHL, which is a rapidly fatal disease, led the authors to observe that, with this regimen, a cure was obtained in > 50% of patients who had low-risk or low-to-intermediate-risk, aggressive NHL.