Margaret Spittle

Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group.

PURPOSE Cytotoxic chemotherapy is frequently required for the more severe manifestations of human immunodeficiency virus (HIV)-related Kaposis sarcoma. Combinations of bleomycin and vincristine (BV) or BV with the addition of doxorubicin (ABV) are the most commonly used regimens against which new treatments may be compared. We report a multicenter phase III study that compared pegylated liposomal doxorubicin (PLD) to the BV combination. PATIENTS AND METHODS We conducted a randomized study that compared PLD 20 mg/m2 with a combination of bleomycin 15 IU/m2 and vincristine 2 mg in 241 patients with HIV-related Kaposis sarcoma. Both regimens were administered by intravenous infusion every 3 weeks for six cycles. RESULTS A total of 121 patients received PLD and 120 patients the BV combination. The response to PLD was superior to BV: 58.7% versus 23.3% (P < .001). Patients who were randomized to receive BV, however, were more likely to terminate treatment early because of an adverse event (26.7% v 10.7%), and fewer completed the full six cycles of treatment (30.8% v 55.4%). Treatment with BV was associated with a significantly higher incidence of peripheral neuropathy (P < .001), whereas PLD treatment was more commonly associated with neutropenia and delays in receiving treatment (P < or = .001). CONCLUSION Pegylated liposomal doxorubicin is an effective treatment for HIV-related Kaposis sarcoma with a higher response rate than the BV combination. It is well tolerated but more myelosuppressive.

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological, immunophenotypic and molecular analysis of six patients.

Summary Background Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is a rare cytotoxic T‐cell lymphoma of the skin. In the World Health Organization classification of T‐cell and natural killer cell lymphoma it is listed as an example of extranodal lymphoma. In practice, however, it is most likely to present to a dermatologist.

Outcome in 34 patients with juvenile-onset mycosis fungoides - A clinical, immunophenotypic, and molecular study

Mycosis fungoides (MF) is predominantly a disease of older patients, but occasionally occurs in children. The aims of the current study were to describe the clinical presentation, pathologic features, and disease progression (DP) in patients who developed MF before age 16 years.

T‐cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement

Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T‐cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T‐cell receptor (TCR) γ‐gene demonstrated by polymerase chain reaction (PCR)/single‐stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high‐dose etoposide (1·6 g/m2) and granulocyte colony‐stimulating factor (G‐CSF). The apheresis products underwent rigorous T‐cell depletion with immunomagnetic methods. Double CD34‐positive and CD4/CD8‐negative selection achieved a median reduction of 3·89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2–14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T‐cell depleted graft. A T‐cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse‐free survival, most patients achieved good disease control at the time of relapse.

Rituximab in cutaneous B-cell lymphoma: a report of two cases

We report two patients with primary cutaneous B‐cell lymphoma who were treated with rituximab, a new anti‐CD20 monoclonal antibody. The first patient, who had a diffuse large B‐cell lymphoma of the lower leg, achieved an 85% improvement. The second patient, who had a primary cutaneous B‐cell lymphoma, which had undergone high‐grade transformation and systemic spread, achieved a minor response of approximately 30%. Both patients subsequently relapsed. The first patient achieved complete clearance with a second course of rituximab given with systemic chemotherapy, but again relapsed. Treatment with rituximab has been reported to produce response rates of 48% in relapsed systemic low‐grade or follicular lymphoma, but there are no previous reports of the use of rituximab in primary cutaneous B‐cell lymphoma.

Autologous Peripheral Blood Stem Cell Transplantation in Tumor-stage Mycosis Fungoides: Predictors of Disease-free Survival

Abstract: Nine patients with mycosis fungoides (age range 27–67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor‐stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G‐CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patients prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short‐lived in four (median disease‐free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post‐PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor‐stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor‐stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell depletion should be restricted to the CD4 subset.

A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T‐cell lymphoma

Background The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non‐Hodgkin’s lymphoma and relapsed chronic lymphocytic leukaemia.

Blastic natural killer cell and extranodal natural killer cell‐like T‐cell lymphoma presenting in the skin: report of six cases from the U.K.

Summary Background Some lymphomas express natural killer (NK)‐cell markers such as the neural cell adhesion molecule, which is recognized by the CD56 antibody. These lymphomas may present in the skin, but do not represent a homogeneous group. The new World Health Organization classification of lymphoma/leukaemia recognizes several types of NK/T‐cell neoplasm, including blastic NK‐cell lymphoma, which characteristically presents with cutaneous lesions.

7 Management of cutaneous lymphoma

Summary The foregoing underlines the advances which have been made in our understanding of cutaneous lymphoma and the areas where further research is needed. With a few noteable exceptions the aim of therapy in CTCL is palliative rather than curative and treatment success is measured in terms of disease-free interval. There is still no evidence that any chemotherapeutic regimen prolongs survival. A possible exception is the effect of photopheresis in Sezary syndrome but our own experience differs from that in the USA and underlines the need to identify patients with clonal disease when defining subjects for study. The combination of genotypic analysis and new treatment methods offers exciting new prospects in the management of patients with cutaneous lymphoma.

Systemic Hodgkin’s lymphoma in a patient with Sézary syndrome

We report a case of a 71‐year‐old male with Sézary syndrome diagnosed in 1996 who subsequently developed systemic Hodgkin’s lymphoma. His only past treatment was bath psoralen plus ultraviolet A. He has since been treated with multiagent chemotherapy (ChlVPP/PABLOE) which induced a remission in his Hodgkin’s disease. Eighteen months later he remains in remission from Hodgkin’s disease but the Sézary syndrome remains active. He has also developed a squamous cell carcinoma on the upper lip. Sézary syndrome is a primary cutaneous T‐cell lymphoma characterized by a malignant proliferation of CD4‐positive cells in the skin and peripheral circulation. The CD4 count may be markedly elevated but this results from expansion of a neoplastic T‐cell clone and there is a relative lymphopenia of normal T cells leading to a degree of immunoparesis. Immunosuppression is known to be associated with an increased rate of malignancies and this may account for the occurrence of Hodgkin’s disease and squamous cell carcinoma in this patient with Sézary syndrome.