A meta-analysis of highly active anti-retroviral therapy for treatment of plasmablastic lymphoma.

BACKGROUND AND OBJECTIVES: Plasmablastic lymphoma is a recently described B-cell derived lymphoma. The prognosis of plasmablastic lymphoma patients is usually poor. We performed a systematic review of the literature on the use of highly active anti-retroviral therapy (HAART) and the prognosis of plasmablastic lymphoma. METHODS: A comprehensive search of relevant databases, including Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library, and the Science Citation Index yielded ten randomized controlled trials. Trials were divided into two groups according to therapy. The rates of plasmablastic lymphoma were analyzed using a fixed-effects model. Sensitivity analyses (on publication type, statistical model) were performed to further detect and evaluate clinically significant heterogeneity. Tests of survival for plasmablastic lymphoma were also performed by using Kaplan-Meier method. RESULTS: Meta-analysis result showed that the prognosis of plasmablastic lymphoma patients was statistically different in the patients receiving HAART in addition to chemotherapy and/or radiotherapy than in the patients receiving the chemotherapy and/or radiotherapy alone (pooled relative risk=3.04; P=.03). Survival analyses also displayed a statistically significant difference (chi-square=6.22, P=.013). CONCLUSION: HAART in addition to chemotherapy and/or radiotherapy is effective in improving the prognosis of plasmablastic lymphoma. However, the small sample sizes increase the likelihood of bias in the studies in this meta-analysis, and therefore, the results should be taken cautiously.

Relationship between the response to treatment and the prognosis of patients with aggressive lymphomas treated with chemotherapy followed by involved-field radiotherapy: radiographic assessment.

OBJECTIVE: We examined the relationship between the response to treatment and prognosis of patients with aggressive lymphoma. METHODS: We reviewed 33 patients with aggressive lymphoma treated with chemotherapy consisting of the CHOP regimen followed by radiotherapy. Twelve patients had Stage I, 13 had Stage II, 6 had Stage III and 2 had Stage IV disease. According to the International Prognostic Index (IPI), 13 had low, 15 had low-intermediate, 2 had high-intermediate and 3 had high IPI. After three to six cycles of chemotherapy, involved-field radiotherapy was performed. We evaluated the response to treatment by computed tomography (CT), magnetic resonance imaging (MRI) and gallium scintigraphy (Ga-67) at the time of completion of chemotherapy and at the time of completion of radiation therapy. The median follow-up period was 48 months (4-80). RESULTS: The 2-year progression-free survival rates of the patients with Ga-67 positive uptake and Ga-67 negative uptake after completion of chemotherapy were 78 and 26% (P = 0.009), respectively. However, there were no statistically significant correlations between progression-free survival and the response after completion of chemotherapy determined by CT (P = 0.75) or MRI (P = 0.19). The response to treatment at the time of completion of overall treatment was not useful for prediction of prognosis. CONCLUSIONS: Ga-67 positive uptake at the completion of chemotherapy before radiotherapy may be associated with poor prognosis.

Radiation therapy after a partial response to CHOP chemotherapy for aggressive lymphomas.

PURPOSE: To analyze the results with involved-field radiotherapy after aggressive lymphomas had decreased in size by 50-99% in response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. METHODS AND MATERIALS: From 1988 through 1996, 294 previously untreated patients with Working Formulation intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these patients achieved, based on international working group guidelines, a partial (50-75%) response (n = 25), or unconfirmed complete (76-99%) response (n = 19) to a median of 6 cycles of chemotherapy. These patients were treated with salvage involved-field radiotherapy (n = 32) or chemotherapy (n = 12), e.g., MINE-ESHAP, without autologous stem-cell rescue (ASCR). RESULTS: Median follow-up was 43 months. Partial responders experienced similar outcomes to unconfirmed complete responders. Local control (4-year rates: 86% vs. 53%, p = 0.009) and progression-free survival (4-year rates: 67% vs. 8%, p < 0.0001), but not overall survival (4-year rates: 70% vs. 50%, p = 0.067) were significantly better in those who received salvage radiotherapy, which was well tolerated. CONCLUSION: Progression-free and overall survival in aggressive lymphoma patients who underwent salvage radiotherapy were similar to results reported for high-dose chemotherapy with ASCR. The role of salvage radiotherapy in partial and unconfirmed complete responders to CHOP chemotherapy justifies examination in a large, cooperative group trial.

Impact of involved field radiotherapy after CHOP-based chemotherapy on stage III-IV, intermediate grade and large-cell immunoblastic lymphomas.

PURPOSE: To analyze the impact of involved field radiotherapy on local control, freedom from progression, and overall survival in patients with clinical Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based induction chemotherapy. METHODS AND MATERIALS: From July 1989 through October 1996, 32 patients with clinical Stage III and 27 patients with clinical Stage IV, intermediate grade, or large-cell immunoblastic lymphomas were prospectively enrolled on two protocols at The University of Texas M. D. Anderson Cancer Center. None had previously undergone treatment for lymphoma. The median patient age was 54 years (range: 26-85 years). There were a total of 172 involved sites of disease at presentation. All 59 patients received CHOP-based chemotherapy. At least six cycles of chemotherapy were delivered to 92% of the patients. Involved field radiotherapy (39.6-40.0 Gy in 20-22 fractions in 74% of cases) was administered to 28/59 (47%) patients beginning 3-4 weeks after chemotherapy. Sites were irradiated at the discretion of the treating physician. Irradiated and nonirradiated groups were compared in terms of maximum pre-chemotherapy tumor size and University of Texas M. D. Anderson Cancer Center tumor score. Kaplan-Meier estimates of local control per patient, freedom from progression, and overall survival for the irradiated and nonirradiated groups were calculated in terms of the stage of disease and treatment delivered. The resulting curves were compared using the log-rank test. The Cox proportional hazards model was used to assess the prognostic significance of tumor size, tumor score, treatment delivered, and stage. RESULTS: The median length of follow-up for all patients was 53 months (range: 4-96 months). The median tumor size at the start of chemotherapy in irradiated patients was 4.5 cm (range: 0-15 cm) versus 3 cm (range: 0-7 cm) in nonirradiated patients (p = 0.004). The irradiated and nonirradiated groups were not significantly different in terms of tumor scores. Radiotherapy improved (p = 0.001) local control (5-year rates: 89% versus 52%) for Stages III and IV combined. This benefit was due to the dramatic improvement (p = 0.0009) in local control for patients with lymphomas measuring > or =4 cm at the start of chemotherapy (5-year rates: 89% for irradiated patients versus 33% for nonirradiated patients). Radiotherapy also improved (p = 0.003) freedom from progression (5-year rates: 85% for irradiated patients versus 51% for nonirradiated patients) for Stages III and IV combined. On multivariate analysis, radiotherapy was the most significant factor affecting local control and freedom from progression. Overall survival was not significantly different (p = 0. 620) between irradiated and nonirradiated patients (5-year rates: 87% versus 81%, respectively). When Stages III and IV were analyzed separately, radiotherapy improved local control and freedom from progression but not overall survival. Radiotherapy was tolerated reasonably well, with the main toxicity being moderate myelosuppression. Eleven out of 12 (92%) patients with recurrent disease at the time of their last follow-up visit were treated initially with chemotherapy alone. CONCLUSION: Involved field radiotherapy improved local control and freedom from progression in patients with > or = 4 cm Stage III-IV, intermediate grade, or large-cell immunoblastic lymphomas that responded to CHOP-based induction chemotherapy. Involved field radiotherapy was tolerated reasonably well.

Reactivation of oral herpes simplex virus: implications for clinical management of herpes simplex virus recurrence during radiotherapy.

Herpes viruses are characterized by their ability to establish and maintain latent infections that can be reactivated. Several stimuli can trigger the reactivation of herpes viruses, which are perhaps best recognized in the recurrent blisters and ulcers associated with herpes simplex virus. We present two clinical cases of reactivation of herpes simplex virus during radiation therapy for management of cancers of the head and neck. Although the role of ionizing radiation in the reactivation of herpes simplex virus has not been established, we review the viral and host events associated with the establishment of orofacial herpes simplex virus infection, latency, and reactivation of the virus. We discuss current models of viral reactivation and suggest directions for further clinical research into the reactivation of orolabial herpes simplex virus during radiotherapy.

Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor.

Among high-grade malignant non-Hodgkin's lymphomas the updated Kiel classification identifies three major B-cell entities: centroblastic (CB), B-immunoblastic (B-IB), and B-large cell anaplastic (Ki-1+) (now termed anaplastic large cell [CD30+], [B-ALC]). The clinical prognostic relevance of this distinction was evaluated in a randomized prospective treatment trial (COP-BLAM/IMVP-16 regimen randomly combined +/- radiotherapy in complete responders) conducted in adult (age 15 to 75) patients with Ann Arbor stage II-IV disease (n = 219) diagnosed by optimal histomorphology (Giemsa staining) and by immunohistochemistry. Overall survival was significantly better in CB lymphoma as compared to B-IB (P = .0002) or B-ALC (P = .046). Relapse-free survival was worse for B-IB (P = .0003) as compared to CB lymphomas. The prognostic differences between CB and B-IB were confirmed by multivariate analyses including the risk factors of the International Index. Overall survival was significantly determined by performance status (P = .0003), serum-LDH (P = .036), and B-IB histology subtype (P = .036). Relapse-free survival was influenced by age (P = .007) and histological subtype (P = .007). Thus, the diagnosis of the CB and B-IB lymphomas by the histological criteria of the Kiel classification was identified as an independent prognostic factor in diffuse large B-cell lymphomas.

Stage I non-Hodgkin's lymphoma treated with doxorubicin-containing chemotherapy with or without radiotherapy.

Seventy-six patients with stage I or IE intermediate-grade or immunoblastic non-Hodgkin's lymphoma were treated with a short course of doxorubicin-containing chemotherapy with (n = 58) or without (n = 18) involved field radiotherapy. Chemotherapy consisted of 3 or 4 cycles of M-BACOD or (bleo-)CHOP. Seventy-two (97%) of the 74 evaluable patients achieved a complete response. The 3-year overall survival was 89%, recurrence-free survival 94%, and lymphoma-specific survival 93%. Patients older than 60 years also had a 3-year lymphoma-specific survival rate of as high as 92%. The International Prognostic Index was associated with overall survival (p = 0.04), but not with lymphoma-specific survival (p = 0.18). We conclude that stages I and IE intermediate-grade or immunoblastic non-Hodgkin's Hodgkin's lymphoma is highly curable if treated with short doxorubicin-containing chemotherapy and involved field radiotherapy.

Multiple superficial basal cell carcinomas (basalomatosis) following cobalt irradiation.

Basalomatosis is an uncommon skin condition characterized by the occurrence of multiple basal cell carcinomas. Many cases reported in the literature have been attributed to arsenic treatment in psoriasis patients. We report a patient with basalomatosis caused by cobalt-60 (60Co) irradiation. A 55-year-old farmer developed 43 basal cell carcinomas 20 years after treatment of an immunoblastoma with 60Co irradiation. All the tumours were located within the radiation fields. Other possible causes of basalomatosis, such as arsenic intoxication and basal cell naevus syndrome, were excluded. The patient's multiple superficial basal cell carcinomas probably represent a late adverse effect of the 60Co irradiation.

Combined chemotherapy and radiotherapy in diffuse large cell immunoblastic lymphoma: a phase II study of CHOP/bleomycin/methotrexate alternating with ifosfamide/methotrexate/etoposide.

The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolidation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% (+/- 9%) and the overall 3-year survival 78% (+/- 9%).