Idiotype immunization following high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma.

The treatment of low- and intermediate-grade subtypes of malignant lymphoma continues to evolve. Mantle cell lymphoma (MCL) accounts for 6% of all non-Hodgkin lymphoma (NHL) and is generally considered incurable. Although high response rates can be achieved with initial chemotherapy, median survival is only 3-4 years. Intensified consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) has been reported to improve progression-free survival (PFS), but most patients eventually relapse. Indolent lymphoma accounts for 35% of all NHL and is associated with a median survival of 9 years. Similar to MCL, it is also generally considered incurable, and the PFS also appears to be improved following HDT/ASCT. We initiated a pilot study to evaluate idiotype (Id) vaccination following HDT and ASCT for patients with MCL, indolent, and transformed NHL to evaluate the ability of Id-keyhole limpet hemocyanin (KLH) to induce immune responses, and to evaluate overall survival (OS) and PFS. We treated 15 patients: 8 with MCL, 4 with follicular lymphoma, 1 with small lymphocytic lymphoma, and 2 with transformed lymphoma. After a median follow-up of approximately 6.3 years (range: 1-9), PFS and OS at 9.05 years from time of ASCT are 59% and 52%, respectively.

Autologous hematopoietic stem cell transplantation as an intensive consolidation therapy for adult patients in remission from acute myelogenous leukemia.

Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myelogenous leukemia (AML). However, its optimal role in treatment for adults in remission has not been clearly established. We performed a retrospective analysis on 45 patients aged 21 to 73 years (median 51 years) with de novo AML who underwent APBSCT stratified by age, complete remission status, and cytogenetic risk. The 5-year disease-free survival (DFS) for all patients was 33.9% (95% confidence interval [CI], 20.1%-53.7%) and overall survival (OS) was 43.6% (CI, 29.2%-62.8%). For patients under the age of 60 years, the 5-year DFS for intermediate and high cytogenetic risk was 53.3% (CI, 23.5%-85.6%) and 50.0% (CI, 16.1%-100.0%); the 5-year OS for patients under the age of 60 years with low, intermediate, and high cytogenetic risk was 80.0% (CI, 40.0%-100.0%), 60.0% (CI, 31.2%-90.7%), and 75.0% (CI, 39.0%-100.0%), respectively. For patients over the age of 60 years, the 5-year DFS and OS for intermediate cytogenetic risk was 21.4% (CI, 7.9%-58.4%) and 21.4% (CI, 7.9%-58.4%). The DFS and OS of these patients are comparable to the historic survival of those who underwent allogeneic stem cell transplantation when adjusted by age. In addition, there was no treatment-related mortality (TRM). We conclude that APBSCT is a reasonable and safe intensive consolidation for patients with AML who do not have a suitable HLA-matched donor.

Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide, sequential granulocyte-macrophage-colony-stimulating factor and granulocyte-colony-stimulating factor, and scheduled commencement of leukapheresis in 225 patients undergoing autologous transplantation.

BACKGROUND: Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. STUDY DESIGN AND METHODS: The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. RESULTS: After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). CONCLUSION: Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.

Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses.

PURPOSE: To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 mug on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated. RESULTS: Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id. CONCLUSION: This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.

Successful perioperative management of factor X deficiency associated with primary amyloidosis.

Acquired bleeding abnormalities are common in patients with primary amyloid light-chain amyloidosis. Factor X deficiency is the most common coagulopathy associated with life-threatening hemorrhagic complications when surgery is indicated. Fresh-frozen plasma (FFP) or prothrombin complex concentrates (PCCs) are the most frequently used blood products in this disease; however, FFP is often ineffective in controlling bleeding and PCCs have a significant risk of thrombosis when used intraoperatively. This report describes a patient with primary amyloidosis and factor X deficiency who underwent hemicolectomy with preoperative and intraoperative administration of recombinant human factor VIIa and postoperative administration of Bebulin (a PCC that contains the highest concentration of factor X). The management was successful with no signs of bleeding postoperatively. To our knowledge, few reports of successful perioperative management of factor X deficiency have been published to date. This is the first case report using recombinant human factor VIIa and Bebulin in the perioperative management of factor X deficiency associated with primary amyloidosis. Recombinant human factor VIIa and Bebulin may allow for successful perioperative management of bleeding disorders in patients with primary amyloidosis.