High-grade Malignant non-Hodgkin's Lymphoma Research Articles

Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma.

Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.

Extranasal T/NK lymphoma with a fatal outcome: A case report

Extranodal T/NK lymphoma (LTNKEN) is a rare and aggressive form of non-Hodgkin lymphoma of high-grade malignancy. A distinction is made between the nasal forms, characterized by primary involvement of the nasal cavity, and the extranasal forms. Primary skin involvement is highly rare. Diagnosis is based on immunohistochemical studies. Treatment includes chemotherapy and radiotherapy. This type of lymphoma has a poor prognosis even with treatment. Herein, we report a Moroccan case of cutaneous T/NK lymphoma in a young patient with a primary cutaneous localization of fatal evolution. Key words: Lymphoma; Extranodal lymphoma; T/NK lymphoma; Non-hodgkin lymphoma

BREAST LYMPHOMA

Primary breast lymphoma is a very rare histological entity of breast cancer. The Clinical and radiological aspects do not present any particular specificities. Diagnosis is often delayed. The treatment is mainly based on chemotherapy. We report the case of a patient with high grade malignant non-Hodgkin lymphoma. The symptomatology was made of breast swelling. The remote extension assessment was negative. The patient received 6 courses of type R mini CHOP chemotherapy followed by three-dimensional radiotherapy with a dose of 30 Gy in 15 fractions for 3 weeks. An echo mammography in between treatment showed: a partial response at 50%. Controle PET CT scan performed 3 weeks after the last cure having objectified: Complete disappearance of the active subcutaneous nodule at the level of the QSE of the right breast. Breast localisation of lymphoma is very rare. His prognosis was considerably improved due to a multidisciplinary approach.

V.-cava-inferior-Thrombose bei Patientin mit Non-Hodgkin-Lymphom und stattgefundener Wirbelsäulenoperation

Complete or partial thrombosis of the inferior vena cava is usually due to pre-existing malformation of the vessel, malignant tumors, ascending thrombosis, or thrombophilic disorders. We report the case of an 81-year-old woman, in whom a partial thrombosis of the vena cava was observed in the CT scan when re-staging was performed after six cycles of R-CHOP because of high-grade malignant non-Hodgkin lymphoma. Before chemotherapy was started, the patient had undergone an operation of the lumbar spine using cement augmentation. Retrospective analysis showed that cement had penetrated a segmental vein and spilled into the vena cava leading to formation of an adhering blood thrombus. The patient was free of symptoms and anticoagulation was started. Spillage of cement frequently occurs in the process of vertebroplasty and kyphoplasty and may result in serious sequelae. As these procedures are increasingly being used, physicians should be aware of these complications if a patient presents with thrombosis of the caval vein or signs of pulmonary embolism.

Somatically mutated immunoglobulin VH genes without intraclonal heterogeneity indicate a post germinal center origin of primary intraocular diffuse large B-cell lymphomas

8072 Background: Primary intraocular lymphoma (PIOL) is a very rare high grade malignant non-Hodgkin lymphoma, usually of the diffuse large B cell lymphoma (DLBCL) type, which presents in the vitreous, retina and/or the optic nerve. Sixty to 80% of patients with PIOL eventually disseminate to the brain, whereas up to 15% of primary central nervous system lymphoma (PCNSL) patients exhibit ocular involvement. For these reasons, PIOL is regarded as a subtype of PCNSL. Analysis of the immunoglobulin heavy chain (VH) sequences in PCNSL tumors demonstrated biased overrepresentation of the VH4–34 gene and indicated derivation of these tumors from highly mutated germinal center (GC) B cells with ongoing mutational activity. Whether PIOL tumors are of similar or different origin is presently unknown. Methods: Immunoglobulin VH genes were examined in vitrectomy specimens of 4 PIOL patients, 1 patient with concomitant PCNSL and 1 patient with systemic DLBCL involving the eye. The extracted DNA was amplified by PCR using VH family specific primers, cloned and sequenced. Results: Seven clonal VH rearrangements belonging to the VH4, VH3 and VH1 families were cloned from the analyzed cases. In concordance with previous reports, the lymphomatous eye infiltrate from the PCNSL patient revealed a mutated clonal VH4–34 gene with intraclonal heterogeneity -a manifestation of active ongoing mutational activity. All the PIOL clonal VH rearrangements also exhibited mutated sequences with homology to the germline sequences ranging between 76 to 95%. However, in contrast to PCNSL, 3 out of 4 PIOL cases exhibited no intraclonal heterogeneity while the remaining case demonstrated ongoing somatic mutations in one of the 2 clonal VH rearrangements detected in this tumor. Interestingly, the clinical course of this patient was highly unusual, since he exhibited systemic dissemination during follow-up. Conclusions: Analysis of VH gene sequences from PIOL tumors indicate a post- GC derivation and suggest that they belong to the activated B cell (ABC)-like subtype of DLBCL. This is in contrast to the GC-origin of closely related PCNSL. No significant financial relationships to disclose.

Human retrovirus type 5 sequences in non-Hodgkin's lymphoma of T cell origin.

DNA of a recently described fifth exogenous retrovirus (HRV-5) has been found in blood samples from patients with autoimmune diseases and lymphoma. We analyzed HRV-5 sequence in DNA extracted from whole blood of 17 patients with T cell non-Hodgkin's lymphoma (NHL) and 186 patients with hematological malignancies other than NHL, using a sensitive PCR technique. While all samples of patients with hematological malignancies other than NHL were negative, 2 of the 17 patients with T cell NHL were HRV-5 DNA positive. Both HRV-5-positive patients had T cell NHL of high-grade malignancy (stage IV) and diffuse distribution of the lymphoma, including infiltration of bone marrow or lung and pleura. The difference in HRV-5 DNA detection frequency between NHL and control groups is significant (p value of 0.0004 judged by the Fisher exact test). These data, together with our previous finding of HRV-5 DNA in three B cell NHL cases, are compatible with an association between HRV-5 and NHL, of both T cell and B cell origin.

Rearranged immunoglobulin light chain genes as minimal residual disease markers in intermediate- and high-grade malignant B cell non-Hodgkin's lymphoma.

Minimal residual disease (MRD) detection in B cell non-Hodgkin's lymphoma (NHL) patients has been shown to be possible using the rearranged heavy (IgH) chain gene as a tumor marker. To explore a second independent tumor marker, we used specific PCR primer sets to identify tumor-specific rearranged Ig light chain (IgL) genes. Rearranged IgL genes were amplified from lymphoma DNA by multiplex PCR using separate primer sets for the Igkappa and the Iglambda genes. They were considered to be of tumor origin if they were monoclonal, and if the same rearrangement was isolated from at least two independent PCR products. From 12 out of 13 intermediate- and high-grade malignant NHL, PCR products could be obtained with IgL specific primers. PCR products from five NHL were studied in detail by cloning and sequencing. The rearranged IgL genes showed 85-100% homology with their closest germ line counterparts. Intraclonal IgL sequence heterogeneity was studied in five lymphomas and detected in only one. Minimal disease was studied in three patients by PCR, followed by Southern hybridization of the PCR product with a lymphoma-specific oligonucleotide probe, which allowed for detection of lymphoma DNA following 1000-fold dilution. Blood samples from one patient, who is in long-term clinical remission, were negative for the lymphoma-specific rearranged Igkappa gene. In the second patient the rearranged Iglambda gene was detected during the first clinical remission, that was followed by a nodal relapse, but not during the second remission, that has been stable for almost 3 years now. The third patient was negative for the rearranged Iglambda gene in blood samples up to 102 months after diagnosis. Circulating lymphoma cells were detected in blood and bone marrow samples which were negative by morphological and immunological criteria. Our studies show that the rearranged IgL gene can be used as a second independent tumor marker in intermediate- and high-grade malignant NHL.

Patients suffering from both Hodgkin's disease and non‐Hodgkin's lymphoma: A clinico‐pathological and immuno‐histochemical population‐based study of 32 patients

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immuno-histochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-I), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma. Int. J. Cancer 71:510-516, 1997. © 1997 Wiley-Liss, Inc.

Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients.

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for non-Hodgkin's lymphomas: a Swedish national prospective study. Swedish Lymphoma Study Group.

One hundred and two patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) in accordance with a prospective protocol. Of 75 patients with high-grade malignant NHL (median age 57 years, range 21-79), 15 patients (20%) obtained a complete response (CR) and 27 patients (36%) a partial remission (PR), giving an overall response rate of 56%. The remissions were usually short when not consolidated with ABMT or radiotherapy. The probability of progression-free survival after 2 years was 13%, and the cause-specific survival was 23%. Of 27 patients with low-grade NHL (median age 46 years, range 37-86), 7% had a CR and 37% a PR giving a response rate of 44%. The remissions were again usually short when not consolidated, and the probability of progression-free survival at two years was 11%, and the cause-specific survival 26%. The main toxicity was hematological with septicemia in 20% of the patients and other severe infections in 19%. Fifteen patients (11 high-grade NHL and 4 low-grade NHL) were consolidated with high-dose therapy followed by ABMT, of whom 6 are in continuous CR. We conclude that MIME can induce remissions in NHL patients, and that the remission rates are comparable with those of many other salvage regimens. The remissions are, however, generally of short duration and need consolidation. There was considerable toxicity therefore patients not suitable for ABMT preferably should be treated with less toxic salvage regimens.

Non-Hodgkin's Lymphomas (NHL)

This synthesis of the literature on radiotherapy for non-Hodgkin's lymphomas is based on 158 scientific articles, including 16 randomized studies, 18 prospective studies, and 90 retrospective studies. These studies involve 14,137 patients. Non-Hodgkin's lymphomas are highly radiosensitive, and local recurrence following radiotherapy is unusual. Radiotherapy probably cures approximately 50% of both low-grade and high-grade malignant NHL at stage I. Involved field is apparently sufficient, however, higher doses are required for high-grade malignant lymphomas. Chemotherapy is recommended for stage II. Consolidation radiotherapy after chemotherapy may increase the number of complete remissions. The value of adjuvant radiotherapy has not been confirmed. Radiotherapy plays a limited role at stages III and IV. Radiotherapy is clearly indicated for extranodal localized disease in the skin and in the orbit of the eye. It is important to identify groups and subgroups in whom radiotherapy alone is sufficient, ie, the risk for distant recurrence is small. MALT lymphoma belongs to this group. Radiotherapy is often valuable in palliative situations.

Primary Non-Hodgkin’s Lymphoma of the Male Urethra

Approximately 15-25% of malignant non-Hodgkin's lymphomas (NHLs) are primarily extranodal and only 2.7% of these are located in the genitourinary tract. Only a few particular cases of primary manifestation of NHL in the urethra have been described, most of them in female patients, whereas a secondary involvement occurs more frequently. In the present case a high-grade malignant NHL of the B-cell type was located in the urethra of a 29-year-old male patient. No other manifestations of NHL could be found. After surgical removal of the urethral neoplasm the patient was treated with combined chemotherapy (6 cycles of the CHOP scheme). Thereafter, reconstruction of the urethra by the island flap method of Duckett was carried out. Two years after diagnosis the patient is alive and in complete remission with good functional and cosmetic results of surgery and a normal sexual life.

Intensive Chemotherapy for High-Risk Patients with High-Grade Malignant Non-Hodgkin Lymphomas: A Pilot Study Using Adriamycin, Cyclophosphamide, Vincristine, Methotrexate, Etoposide, and Dexamethasone (ACOMED Protocol)

<i>Background</i>: In high-grade malignant non-Hodgkin lymphomas (NHL), prognostic risk is assessable by a series of initial parameters but adequate treatment approaches to high-risk patients remain to be established. The aim of the present study was therefore to evaluate the feasibility and efficiency of the intensified induction chemotherapy regimen ACOMED for poor prognosis patients. <i>Patients and Methods</i>: Unpretreated patients with high-grade malignant NHL (Kiel classification) presenting with Ann Arbor stage Il-IV disease and at least one prognostic risk factor (stage III/IV, serum LDH > normal, performance status ECOG > 2, bulky disease > 10 cm) were treated with the ACOMED regimen consisting of four courses of adriamycin 25 mg/m2 i.v. days 4-5, cyclophosphamide 250 mg/m2 i.v. days 1-5, vincristine 2 mg i.v. absolute day 1, methotrexate 500 mg/m2 i.v. day 1 with leucovorin-rescue, etoposide 100 mg/m2 i.v. days 1-5, dexamethasone 10 mg/m2 p.o. days 1-5, supported by G-CSF and repeated on day 21. <i>Results</i>: Of 44 patients recruited to the study, 31 have already completed treatment and are thus fully evaluable. Complete remissions were obtained in 25/31 (81%) of the patients; 4/25 (16%) relapsed, median observation time for all is 12 (3-18) months. The major side effect was mucositis occurring as WHO grade 4 in 30% of the patients in cycle 1, gradually decreasing in incidence and severity in further cycles but leading to an early discontinuation of the protocol and a switch to COP-BLAM or CHOP in 8/31 patients after 2 (1-3) cycles. Infections were rarely severe and myelotoxicity of WHO grade 4, though observed in one-third of the cycles, was only of short duration. <i>Conclusions</i>: ACOMED thus presents a highly effective regimen for remission induction in NHL poor-risk patients with longer observation periods required for the final judgement on remission stability. However, modifications of supportive care to ameliorate mucositis do seem to be desirable.

Randomized, Double-Blind, Placebo-Controlled, Phase III Study of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor as Adjunct to Induction Treatment of High-Grade Malignant Non-Hodgkin's Lymphomas

We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.

A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome.

High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.

Cyclic alternating chemotherapy of high-grade malignant non-Hodgkin lymphomas with VIM-Bleo and CHOP

Between 1986 and 1988, 81 patients with high grade malignant non-Hodgkin lymphoma according to the Kiel classification were treated with the VIM-Bleo/CHOP-regimen: etoposide 100 mg/m 2 intravenously on days 1–3, ifosfamide 1.5 g/m 2 intravenously days 1–5 with mesna for prophylaxis of cystitis, methotrexate 30 mg/m 2 intravenously on days 3, bleomycin 10 mg intravenously on days 8 and 15, cyclophosphamide 750 mg/m 2 day 22, doxorubicin 50 mg/m 2 day 22, vincristine 1.4 mg/m 2 on day 22, and prednisolone 100 mg postoperatively on days 1–5 and 22–26. Cycles were repeated four times beginning on day 43. Regions with bulky disease were irradiated after chemotherapy. 36 patients (44%) had stage II, 12 (15%) stage III and 33 (41%) stage IV disease. B-symptoms were present in 49% of patients. Serum lactate dehydrogenase activity was elevated in 53%. Overall, 59 patients (73%) achieved a complete and 14 (17%) a partial remission. 8 (9%) had stable or progressive disease. After a median follow up of 30 months thus far, probability of long-term relapse free survival is 66% for patients in complete remission. Overall survival is 72% at 24 months. Toxicity from treatment was very low with leukopenia being the main side effect. Major infections were observed in only 2% of cycles with one treatment related death. VIM-Bleo/CHOP is a well tolerated regimen with remission rates in the range of other, more toxic regimens. However, cyclic alternating treatment did not improve results as compared with repeated treatment with a single standard protocol.

Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade Non-Hodgkin's Lymphoma (NHL): The 1980–1985 EORTC trial

A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.

Mitoxantrone, etoposide, cytarabine and prednisone as salvage therapy for refractory non‐Hodgkin lymphoma (NHL) and alternated with CHOP in previously untreated patients with NHL

The treatment of relapsing or refractory high-grade malignant non-Hodgkin lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician. In this study, 29 patients with relapsing or refractory high- or refractory low-grade malignant NHL received a combination of mitoxantrone 12 mg/m2 i.v. on days 1-2, cytarabine 100 mg/m2 i.v., b.d. d 1-2, etoposide 100 mg/m2 i.v. d 1-3 and prednisone 100 mg/m2 orally d 1-3 (ENAP). An overall response rate of 55% encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45 previously untreated NHL patients (35 with high-grade and 10 with "aggressive" low-grade malignant NHL). All patients responded with a complete remission rate (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69 and 22%, respectively. Myelosuppression was pronounced and fever of unidentified origin and documented infections followed 59% of all cases given ENAP courses. In the last 19 previously untreated patients mitoxantrone was given at a dose of 10 mg/m2 on d 1 and cytarabine 100 mg i.v., b.d. during d 1-2. Nonhematologic toxicity was mild. We conclude that this novel chemotherapy program is effective both as first-line and salvage treatment in patients with high-grade malignant NHL. Furthermore, ENAP appears clinically to be partly non-cross resistant with CHOP chemotherapy. The dose-limiting toxicity is myelosuppression. The combination should be explored as primary therapy in combination with other chemotherapy or radiotherapy programs.

Phase II study of lomustine, cytarabine, mitoxantrone, and prednisone (CAMP) combination chemotherapy for doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphoma.

A phase II study was conducted to evaluate the efficacy and toxicity of lomustine, cytarabine, mitoxantrone and prednisone (CAMP) chemotherapy in doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphomas (NHL). Among 30 patients, the complete remission rate was 27% (duration: 10, 16, 22, 35, 35+, 42+, 51+, 55+ months) and the partial remission rate was 20%. Median survival for complete responders was more than 4 years. The best responses were seen in patients with relapsed NHL compared to those with primary refractory NHL. Toxicity was mainly related to myelosuppression. The results suggest that the CAMP schedule can be applied on an outpatient basis with satisfactory efficacy in patients with relapsing intermediate- and high-grade malignant NHL.

Clinical course and pathologic features of conjunctival non-Hodgkin's lymphoma

Six patients with conjunctival non-Hodgkin's lymphoma (NHL) were evaluated. In all six cases the conjunctiva was the primary site of clinical presentation; four cases involved low-grade malignancy and two, intermediate-grade malignancy, according to the International Working Formulation. The disease developed within a short period of time to stage IV. The poor response to therapy revealed a worse prognosis than would be expected according to the histopathologic classification. Four of the six patients died of NHL, three of them within 15 months. Comparison of these 6 cases with a group of 15 patients with orbital NHL revealed a much better prognosis in the latter patients. In spite of the fact that 4 of the 15 orbital cases showed NHL of high-grade malignancy, only 2 of them died of the lymphoma. Therefore, conjunctival NHL requires a fast and adequate diagnostic and therapeutic approach.