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Jennifer A Kanakry, Yvette L Kasamon,
Christopher D Gocke,
Hua-Ling Tsai,
Janice Davis-Sproul,
Nilanjan Ghosh,
Heather Symons,
Javier Bolaños-Meade,
Douglas E Gladstone,
Lode J Swinnen,
Leo Luznik,
Ephraim J Fuchs,
Richard J Jones,
Richard F Ambinder
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ABSTRACT: BACKGROUND: The role of allogeneic blood or marrow transplantation (alloBMT) for peripheral T-cell lymphoma (PTCL) remains to be defined. There is growing interest in reduced-intensity conditioning (RIC) regimens and/or utilization of HLA-haploidentical (haplo) grafts given concerns about treatment-associated toxicities and donor availability. METHODS: We reviewed the outcomes of 44 consecutive, related donor alloBMTs for PTCL performed at Johns Hopkins Hospital from 1994-2011, including 18 RIC/haplo alloBMTs. RESULTS: Patients receiving RIC (n=24) were older with median age of 59 years (range 24-70) than patients receiving myeloablative conditioning (MAC, n=20) with median age of 46 years (range 18-64), p=0.01. The median age at RIC/haplo alloBMT was 60 years. The estimated 2-year progression-free survival (PFS) was 40% (95% confidence interval (CI) 26-55%) and overall survival (OS) was 43% (95% CI 28-59%). In older patients (> 60, n=14), the estimated 2-year PFS and OS were 38% (CI 18-79%) and 45% (CI 24-86%). On unadjusted analysis, there was a tendency towards superior outcomes for alloBMT in first remission versus beyond first remission, with an estimated 2-year PFS of 53% (95% CI 33-77%) versus 29% (95% CI 9-45%), p=0.08. On competing risk analysis, the 1-year cumulative incidence of relapse was 38% for MAC/HLA-identical alloBMTs and 34% for RIC/haplo alloBMTs. Estimated 1-year non-relapse mortality was 10% for MAC and 8% for RIC (11% for RIC/haplo alloBMT). On unadjusted landmark analysis, patients with acute grade II-IV or chronic GVHD had a 17% probability of relapse (95% CI 0-39%), compared to 66% (95% CI 48-84%) in patients without GVHD, p=0.04. CONCLUSIONS: Utilization of RIC and alternative donors expands treatment options in PTCL to those who are older and unable to tolerate high-dose conditioning, with outcomes comparable to approaches using myeloablative regimens and HLA-matched donors. AlloBMT may be appropriate in first remission in select high-risk cases.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2013; · 3.15 Impact Factor
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ABSTRACT: The presence of donor HLA-specific antibodies (DSA) increases engraftment failure risk in partially-HLA mismatched, or HLA-haploidentical, allogeneic marrow (alloBMT) transplantation. As pre-existing sensitization to HLA antigens is not well characterized among candidates for HLA-haploidentical alloBMT, we retrospectively evaluated both the incidence and relative strength of DSA in this patient population. Based on correlations of solid phase antibody assays on the Luminex™ platform with actual crossmatch tests, DSA were characterized as weak for results that were consistent with negative flow cytometric crossmatch results or as moderate to strong for results consistent with positive flow cytometric or cytotoxicity crossmatches. 296 alloBMT candidates (111 [37.5%] female) were evaluated. DSA were detected in 43 (14.5%) candidates, mostly among female candidates (42.9% female vs. 12.5% male). Moderate to strong DSA strength was more frequently encountered when directed against haploidentical donors as compared to mismatched unrelated donors. DSA were most commonly detected in female patients directed against their children. Because the presence of DSA has been considered prohibitive for HLA mismatched alloBMT, we additionally report a desensitization methodology used to reduce DSA to negative or weak levels. i.e., levels well below those detectable in a flow cytometric crossmatch. Nine patients without other available donors underwent desensitization. Eight reduced their DSA to negative or weak levels proceeded to alloBMT and achieved full donor engraftment. These data support routine DSA evaluation in all patients considered for mismatched alloBMT; however, for patients with no other viable options, desensitization to weak or negative DSA levels may afford the opportunity for successful transplantation.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2013; · 3.15 Impact Factor
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Yvette L Kasamon,
Robert A Brodsky,
Michael J Borowitz,
Richard F Ambinder,
Pamela A Crilley,
Steve Y Cho,
Hua-Ling Tsai,
B Douglas Smith,
Douglas E Gladstone,
Hetty E Carraway,
Carol Ann Huff,
William H Matsui,
Javier Bolaños-Meade,
Richard J Jones,
Lode J Swinnen
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ABSTRACT: Older patients with Burkitt lymphoma/leukemia (BL) have inferior outcomes. Because cyclophosphamide is highly active in BL and can be dose-escalated without stem-cell rescue, we designed a short, cyclophosphamide-intensive regimen without anthracyclines for patients aged ≥ 30 with untreated, non-HIV-associated BL/atypical BL. Two cycles involving cyclophosphamide 1500 mg/m(2), vincristine, rituximab, prednisone, methotrexate 3 g/m(2), and intrathecal cytarabine were delivered 2 weeks apart, followed by intensification with high-dose cyclophosphamide (50 mg/kg/day for 4 days) and rituximab. Of 21 patients, median age 53 (range, 34-75), 71% had stage IV, 95% were high-risk and 29% had performance status 3-4. Response occurred in all evaluable patients post-cycle 2 and in 76% post-intensification. Five non-relapse deaths occurred (four before intensification). The estimated 1-year and 3-year event-free survival was 52%; 1-year and 3-year overall survival was 57%. Seventeen (81%) received intensification (median 30 days to intensification). Brief, anthracycline-sparing, intensive cyclophosphamide (BASIC) therapy yields durable remissions in poorer-risk BL/atypical BL.
Leukemia & lymphoma 07/2012; · 2.40 Impact Factor
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ABSTRACT: Radiotherapeutic advances have contributed to the evolution of Hodgkin's lymphoma (HL) treatment paradigms. A reduction in radiation therapy (RT) field size and dose has the potential to significantly impact the therapeutic ratio by diminishing late toxicities while maintaining curability. Substantial progress in risk stratification has contributed to the development of tailored RT strategies which address both field design as well as dose. Technologic improvements have also enhanced the ability to adapt the RT technique to the individual patient. The refinement of the RT approach and its incorporation into current combined modality strategies in adult classical HL is the subject of ongoing investigation and is critically reviewed.
Critical reviews in oncology/hematology 03/2012; 84(1):71-84. · 5.27 Impact Factor
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Yvette L Kasamon,
Heather A Jacene,
Christopher D Gocke,
Lode J Swinnen,
Douglas E Gladstone,
Brandy Perkins,
Brian K Link,
Leslie L Popplewell,
Thomas M Habermann,
Joseph M Herman,
William H Matsui,
Richard J Jones,
Richard F Ambinder
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ABSTRACT: In classical Hodgkin lymphoma, circulating clonotypic malignant cells express CD20, which potentially explains the observed activity of rituximab. This multicenter phase 2 study investigated the combination of rituximab-ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage II-IV untreated classical Hodgkin lymphoma. A goal was to assess the behavior of circulating clonotypic B cells clinically. Of 49 evaluable patients, 69% had stage IIB-IV disease; 8% had CD20(+) Hodgkin and Reed-Sternberg cells. Rituximab-ABVD was generally well tolerated. Delivered relative dose intensity was 94% for AVD and 79% for bleomycin. After 6 cycles, 81% of patients were in complete remission. Only 8% received radiation therapy. The actuarial 3-year event-free and overall survival rates were 83% and 98%, respectively. EBV copy number in plasma fell dramatically during cycle 1 in patients with EBV(+) tumors. Persistence of detectable circulating clonotypic B cells was associated with a greater relapse frequency (P < .05). Rituximab-ABVD and clonotypic B cells warrant additional study in classical Hodgkin lymphoma.
Blood 02/2012; 119(18):4129-32. · 9.90 Impact Factor
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ABSTRACT: Hematopoietic stem cell transplantation provides the only potential curative option in many patients with hematological malignancies. Finding a suitably matched donor in a timely manner is often difficult. However, most patients have a partially HLA-mismatched (HLA-haploidentical) first-degree relative readily available. Historically, HLA-haploidentical bone marrow transplantation (BMT) has been considered extremely high risk due to high rates of life-threatening graft-versus-host disease (GVHD) and non-relapse mortality (NRM). Modifications of the stem cell graft, such as T-cell depletion, have resulted in poor rates of engraftment. We have recently completed a phase II clinical trial of nonmyeloablative HLA-haploidentical hematopoietic BMT followed by post-transplantation high-cyclophosphamide. High-dose cyclophosphamide has been shown to create immunogenic tolerance by specifically killing activated mature T-cells. As a result, alloreactive T-cells in the donor graft are selectively destroyed thereby decreasing the incidence of severe GVHD. As well, host-versus-graft reactive T-cells are also selectively eliminated thereby increasing rates of engraftment. Among 210 patients with hematological malignancies receiving nonmyeloablative, HLA-haploidentical BMT with post-transplantation cyclophosphamide, the rate of sustained donor cell engraftment has been 87%. The cumulative incidence of grade 2-4 acute GVHD is 27%, grade 3-4 acute GVHD is 5% and chronic GVHD is 15%. Interestingly, increasing HLA disparity between donor and recipient was not associated with increasing incidence of GVHD or decreased event-free survival. Nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide seems to be a promising, potentially curative, option for patients with hematological malignancies who either lack an HLA-matched related or unrelated donor, or in whom a myeloablative preparative regimen is contraindicated due to significant co-morbidities or history of extensive pre-treatment.
Best practice & research. Clinical haematology 09/2011; 24(3):359-68. · 3.13 Impact Factor
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ABSTRACT: Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post-transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini-haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies.
Pediatric reports 06/2011; 3 Suppl 2:e15.
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ABSTRACT: Autologous blood or marrow transplantation (ABMT) for low-grade lymphomas can prolong event-free survival (EFS) but requires long-term follow-up. We report one of the longest follow-ups to a prospective transplantation study in such diseases. On a phase II study, 80 patients with low-grade, transformed, or mantle cell lymphoma received ABMT with 4-hydroperoxycyclophosphamide (4-HC) purging as part of initial or salvage therapy. Diagnoses included nontransformed follicular lymphoma in 63% and transformed lymphoma in 15%. With 16.6-year median follow-up for survival, actuarial 10-year EFS and overall survival (OS) were 34% (95% confidence interval [CI], 25%-46%) and 45% (35%-57%). Median EFS and OS were 3.0 and 8.0 years. Early nonrelapse mortality incidence was 8%; myelodysplastic syndrome or leukemia incidence was 4%. Most relapses occurred within 3 years, with a median time to diagnosis of relapse of 1.8 years (range: 0.1-15.6 years). On multivariate analysis, age >50 years, ≥3 prior chemotherapy regimens, and ABMT after relapse were associated with significantly inferior survival. Fifteen patients (19%) were event-free >15 years after transplantation, raising the possibility of a plateau in the progression-free survival curve. Thus, 4-HC-purged ABMT can produce extended remissions in a subgroup of patients with indolent lymphomas.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2011; 17(3):365-73. · 3.15 Impact Factor
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Yvette L Kasamon
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ABSTRACT: The use of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for response assessment in lymphoma is now widespread. Prognostic information obtained from PET performed after two to three cycles of chemotherapy may guide more individualized, risk-adapted therapeutic strategies. Progress in the risk stratification of Hodgkin's lymphoma through midtreatment PET is reviewed, with a focus on management implications in newly diagnosed and relapsed disease. How to tailor treatment on the basis of the interim PET result is not yet defined but is the subject of ongoing trials.
Advances in Hematology 01/2011; 2011:271595.
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B Douglas Smith, Yvette L Kasamon,
Jeanne Kowalski,
Christopher Gocke,
Kathleen Murphy,
Carole B Miller,
Elizabeth Garrett-Mayer,
Hua-Ling Tsai,
Lu Qin,
Christina Chia,
Barbara Biedrzycki,
Thomas C Harding,
Guang Haun Tu,
Richard Jones,
Kristen Hege,
Hyam I Levitsky
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ABSTRACT: Chronic myeloid leukemia (CML) can be responsive to T-cell-mediated immunity. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) is a GM-CSF producing vaccine derived from a CML cell line that expresses several CML-associated antigens. A pilot study was developed to determine if K562/GM-CSF immunotherapy could improve clinical responses to imatinib mesylate (IM) in patients with chronic myeloid leukemia.
Patients with chronic phase CML who achieved at least a major cytogeneic response but remained with persistent, measurable disease despite one or more years on imatinib mesylate were eligible. Each was given a series of four vaccines administered in three-week intervals, with or without topical imiquimod, while remaining on a stable dose of imatinib mesylate. CML disease burden was measured serially before and after vaccination.
Nineteen patients were vaccinated, with a median duration of previous imatinib mesylate therapy of 37 (13-53) months. Mean PCR measurements of BCR-ABL for the group declined significantly following the vaccines (P = 0.03). Thirteen patients had a progressive decline in disease burden, 8 of whom had increasing disease burden before vaccination. Twelve patients achieved their lowest tumor burden measurements to date following vaccine, including seven subjects who became PCR-undetectable.
K562/GM-CSF vaccine appears to improve molecular responses in patients on imatinib mesylate, including achieving complete molecular remissions, despite long durations of previous imatinib mesylate therapy.
Clinical Cancer Research 01/2010; 16(1):338-47. · 7.74 Impact Factor
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Yvette L Kasamon,
Leo Luznik,
Mary S Leffell,
Jeanne Kowalski,
Hua-Ling Tsai,
Javier Bolaños-Meade,
Lawrence E Morris,
Pamela A Crilley,
Paul V O'Donnell,
Nancy Rossiter,
Carol Ann Huff,
Robert A Brodsky,
William H Matsui,
Lode J Swinnen,
Ivan Borrello,
Jonathan D Powell,
Richard F Ambinder,
Richard J Jones,
Ephraim J Fuchs
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ABSTRACT: Although some reports have found an association between increasing HLA disparity between donor and recipient and fewer relapses after allogeneic blood or marrow transplantation (BMT), this potential benefit has been offset by more graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). However, the type of GVHD prophylaxis might influence the balance between GVHD toxicity and relapse. The present study analyzed the impact of greater HLA disparity on outcomes of a specific platform for nonmyeloablative (NMA), HLA-haploidentical transplantation. A retrospective analysis was performed of 185 patients with hematologic malignancies enrolled in 3 similar trials of NMA, related donor, haploidentical BMT incorporating high-dose posttransplantation cyclophosphamide for GVHD prophylaxis. No significant association was found between the number of HLA mismatches (HLA-A, -B, -Cw, and -DRB1 combined) and risk of acute grade II-IV GVHD (hazard ratio [HR] = 0.89; P = .68 for 3-4 vs fewer antigen mismatches). More mismatching also had no detrimental effect on event-free survival (on multivariate analysis, HR = 0.60, P = .03 for 3-4 vs fewer antigen mismatches and HR = 0.55, P = .03 for 3-4 vs fewer allele mismatches). Thus, greater HLA disparity does not appear to worsen overall outcome after NMA haploidentical BMT with high-dose posttransplantation cyclophosphamide.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2009; 16(4):482-9. · 3.15 Impact Factor
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Yvette L Kasamon,
Richard L Wahl,
Harvey A Ziessman,
Amanda L Blackford,
Steven N Goodman,
Caroline A Fidyk,
Kathryn M Rogers,
Javier Bolaños-Meade,
Michael J Borowitz,
Richard F Ambinder,
Richard J Jones,
Lode J Swinnen
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ABSTRACT: In newly diagnosed aggressive non-Hodgkin lymphoma (NHL), a positive midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography (PET) scan often carries a poor prognosis, with reported 2-year event-free survival (EFS) rates of 0% to 30% after standard therapy. To determine the outcome of early treatment intensification for midtreatment PET-positive disease, a phase II trial of risk-adapted therapy was conducted. Fifty-nine newly diagnosed patients, 98% with B cell lymphoma, had PET/CT performed after 2 or 3 cycles of first-line chemotherapy. Those with negative PET on semiquantitative visual interpretation completed standard therapy. Those with positive PET received platinum-based salvage chemotherapy, high-dose therapy, and autologous stem cell transplantation (ASCT). Midtreatment PET was positive in 33 (56%); 28 received ASCT with an actuarial 2-year EFS of 75% (95% confidence interval, 60%-93%). On intention-to-treat analysis, 2-year EFS was 67% (53%-86%) in all PET-positive patients and 89% (77%-100%) in PET-negative patients. No association was found between the International Prognostic Index category and the midtreatment PET result. The favorable outcome achieved here in historically poor-risk patients warrants further, more definitive investigation of treatment modification based on early PET scanning.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2009; 15(2):242-8. · 3.15 Impact Factor
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Richard J Jones,
Christopher D Gocke, Yvette L Kasamon,
Carole B Miller,
Brandy Perkins,
James P Barber,
Milada S Vala,
Jonathan M Gerber,
Lan L Gellert,
Mark Siedner,
M Victor Lemas,
Sarah Brennan,
Richard F Ambinder,
William Matsui
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ABSTRACT: Although Hodgkin and Reed-Sternberg (HRS) cells are B lymphoid cells, they are unlike any normal cells of that lineage. Moreover, the limited proliferative potential of HRS cells belies the clinical aggressiveness of Hodgkin lymphoma (HL). More than 20 years ago, the L428 HL cell line was reported to contain a small population of phenotypic B cells that appeared responsible for the continued generation of HRS cells. This observation, however, has never been corroborated, and such clonotypic B cells have never been documented in HL patients. We found that both the L428 and KM-H2 HL cell lines contained rare B-cell subpopulations responsible for the generation and maintenance of the predominant HRS cell population. The B cells within the HL cell lines expressed immunoglobulin light chain, the memory B-cell antigen CD27, and the stem cell marker aldehyde dehydrogenase (ALDH). Clonal CD27(+)ALDH(high) B cells, sharing immunoglobulin gene rearrangements with lymph node HRS cells, were also detected in the blood of most newly diagnosed HL patients regardless of stage. Although the clinical significance of circulating clonotypic B cells in HL remains unclear, these data suggest they may be the initiating cells for HL.
Blood 03/2009; 113(23):5920-6. · 9.90 Impact Factor
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ABSTRACT: Multiple immune evasion strategies characterize the pathobiology of Hodgkin's lymphoma. These must be considered when developing and testing immunotherapeutic approaches for this disease. The clinical experience with adoptive immunotherapy of Epstein-Barr virus positive tumors, and with monoclonal antibodies directed against CD30, CD20, and other antigens, is herein reviewed.
Critical Reviews in Oncology/Hematology 06/2008; 66(2):135-44. · 4.41 Impact Factor
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ABSTRACT: The prognostic utility of midtreatment fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG PET) has become widely appreciated in aggressive B-cell non-Hodgkin's lymphoma and, more recently, in Hodgkin's lymphoma. Outcomes based on midtreatment FDG PET performed during primary and salvage therapy are reviewed and management strategies considered, with a focus on treatment intensification for poor-risk disease as identified by metabolic imaging.
PET, when performed after as few as two cycles of primary chemotherapy, is strongly prognostic in certain aggressive lymphomas and provides information independently from validated prognostic indices. What constitutes a positive or negative scan is not always clear, particularly if there is minimal tracer uptake, and the causes of false positive and false negative scans must be considered. How to tailor therapy based on the midtreatment PET result is the focus of current trials and is presently being defined for both Hodgkin's and non-Hodgkin's lymphoma.
Early PET has the strong potential to improve clinical outcomes by sparing good-risk patients from overly aggressive treatments, and by more accurately identifying poor-risk patients so as to guide changes in management. Treatment modifications on the basis of midtreatment PET are presently best made in clinical trial settings.
Current opinion in oncology 04/2008; 20(2):206-19. · 4.09 Impact Factor
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Javier Bolaños-Meade,
Elizabeth Garrett-Mayer,
Leo Luznik,
Viki Anders,
Jennifer Webb,
Ephraim J Fuchs,
Carol Ann Huff,
William Matsui,
Ivan M Borrello,
Robert Brodsky, Yvette L Kasamon,
Lode J Swinnen,
Ian W Flinn,
Richard F Ambinder,
Richard J Jones,
Allan D Hess,
Georgia B Vogelsang
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ABSTRACT: The results of blood or marrow transplantation in patients with chemorefractory aggressive lymphoma, that is, those not responding to conventional-dose chemotherapy at the time of transplant, have been poor. The relapse rate has been high after autologous bone marrow transplant, whereas allogeneic transplantation has been associated with excessive transplant-related toxicity. Administration of cyclosporine after autologous transplantation can induce an autoreactive syndrome that resembles graft-versus-host disease (GVHD). This syndrome, named autologous graft-versus-host disease, has clear antitumor activity in animal models that can be enhanced by the addition of cytokines such as gamma-interferon and interleukin-2. A randomized, prospective study was conducted to evaluate the antitumor effect of autologous graft-versus-host disease induced with cyclosporine, and augmented by the administration of gamma-interferon and interleukin-2 in patients with chemorefractory Hodgkin and aggressive non-Hodgkin lymphomas. Fifty-one patients were randomized, 24 to the autologous GVHD induction arm, and 27 to the noninduction arm after autologous transplant using mobilized peripheral blood stem cell (PBSC) grafts. There were no differences in treatment-related mortality, overall and event-free survival (OS, EFS) between both groups; however, in the induction arm, GVHD developed only in 4 patients. The administration of oral cyclosporine followed by interleukin-2 and gamma-interferon is generally not well tolerated, and does not appear to be an effective method to induce autologous GVHD in patients receiving autologous PBSC grafts.
Biology of Blood and Marrow Transplantation 11/2007; 13(10):1185-91. · 3.87 Impact Factor
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ABSTRACT: Fludarabine-based regimens have become an increasingly popular first-line approach for symptomatic patients with chronic lymphocytic leukemia. Compared with chlorambucil, fludarabine alone or in combination with cyclophosphamide or rituximab yields higher response rates, higher complete remission rates, and more durable progression-free survival. Immunotherapy and chemoimmunotherapy also have the potential to increase the depth of remission as assessed by flow cytometry or molecular techniques. An overall survival advantage with any one particular regimen has not yet been demonstrated. Progress with fludarabine-based regimens, monoclonal antibodies, chemoimmunotherapy, and high-dose therapy for previously untreated patients is reviewed. Fluorescent in situ hybridization and immunoglobulin variable heavy-chain sequencing now permit more individualized risk assessment. Examples of possible treatment algorithms based on risk category are explored. How to tailor treatment based on these newer prognostic factors remains a central, as yet unanswered management question.
Blood Reviews 06/2007; 21(3):143-56. · 5.36 Impact Factor
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Yvette L Kasamon
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ABSTRACT: Mantle cell lymphoma is a generally incurable disease for which blood or marrow transplantation is frequently considered. This review assesses the more recent literature on high-dose therapeutic approaches for mantle cell lymphoma.
The benefit of transplantation is most apparent in first remission. Autologous transplantation can prolong event-free and possibly overall survival, although no plateau has been demonstrated in the survival curve. A randomized controlled trial demonstrated a significant event-free survival advantage to upfront autologous transplantation compared with interferon maintenance. The relative merit of autologous versus allogeneic transplantation remains to be better defined.
The role of transplantation for mantle cell lymphoma is controversial, as the impact on overall survival is unclear. Transplantation should be considered early in the disease course. Elimination of minimal residual disease through in-vivo purging of stem cells may translate into more durable remissions. Nonmyeloablative allogeneic transplantation and high-dose radioimmunotherapy are topics of ongoing investigation.
Current Opinion in Oncology 04/2007; 19(2):128-35. · 4.10 Impact Factor
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ABSTRACT: Imaging with 18F-FDG PET is increasingly accepted as a valuable tool for lymphoma management. A recent shift in the use of PET and PET/CT in medical practice has become evident. We selected aggressive lymphomas as a platform for the discussion of these imaging modalities in oncology patients and the resulting management questions.
On the basis of our clinical experience and a review of the literature, we evaluated the emerging role of 18F-FDG PET in staging, response assessment, risk stratification, and tailored therapy. We explored the biologic meaning of true-positive or true-negative PET results in assessing tumor killing and the implications for risk-adapted therapy of lymphoma.
PET/CT improves the accuracy of staging and response assessment over that of conventional anatomic imaging. The strong prognostic value of PET for aggressive lymphomas is established, whether the imaging is performed at the end of therapy or after only a few cycles of chemotherapy. How to modify therapy on the basis of PET results is not yet established, although it is clear that high-risk patient subsets can be reliably identified.
PET/CT improves the accuracy of staging and response assessment over that of CT alone. A negative midtreatment PET result does not indicate the absence of a viable tumor or that therapy can be abbreviated or reduced in intensity. Similarly, a positive PET result does not necessarily indicate a viable tumor or that extending or intensifying treatment will benefit the patient. In assessing response, it is possible that prognosis rests not only on whether the PET result is positive or negative but also on the intensity of the signal. Although the prognostic value of PET for lymphoma is now clear, how to tailor therapy accordingly is a separate matter that requires further investigation.
Journal of Nuclear Medicine 02/2007; 48 Suppl 1:19S-27S. · 6.38 Impact Factor
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ABSTRACT: Fludarabine and cyclophosphamide is an effective combination but increases the risk of opportunistic infections due to depressed lymphocyte counts. In an attempt to preserve CD4 counts, we conducted a phase I, double-blind, placebo-controlled trial of recombinant interleukin-2 (IL-2) added to fludarabine and cyclophosphamide in patients with treatment-naive indolent lymphomas or chronic lymphocytic leukemia.
Subcutaneous IL-2 (days 1-21 of each 28-day cycle) was combined with cyclophosphamide (600 mg/m2, day 8) and fludarabine (20 mg/m2, days 8-12) at four dose levels: 0.8, 1.0, 1.2, and 1.4 x 10(6) IU/m2/d. IL-2 dose was escalated in cohorts of four to six patients, with one patient per cohort receiving placebo.
Twenty-three patients, median age 50, were enrolled, of whom 30% had chronic lymphocytic leukemia/small lymphocytic lymphoma and 52% had follicular lymphomas. The combination was generally well tolerated, with mainly hematologic toxicities. CD4 counts typically declined substantially during the early weeks of treatment and remained suppressed for months afterward. In the 18 evaluable patients who received IL-2, the mean absolute CD4 count was 999 cells/microL (range, 97-3,776) pretreatment, 379 cells/microL (range, 54-2,599) at day 14, and 98 cells/microL (range, 17-291) at end of treatment. In longitudinal linear models, the changes in CD4 counts were not significantly different across IL-2 dose levels.
The addition of low-dose IL-2 to fludarabine and cyclophosphamide does not seem immunoprotective. New approaches are needed to reduce the cellular immunosuppression and infectious complications associated with purine analogues.
Clinical Cancer Research 01/2006; 11(23):8413-7. · 7.74 Impact Factor
