Role Of High-dose Therapy Research Articles

LONG-TERM OUTCOME OF PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA TREATED WITH FIRST-LINE INTENSIVE CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANTATION

Peripheral T-cell lymphomas (PTCL) are infrequent subtypes of non-Hodgkin's lymphomas. The clinical course is aggressive and the median survival is about 2-3 years. An optimal first-line chemotherapy protocol has not been established and the role of high-dose therapy with autologous stem cell transplantation (ASCT) is still unclear. To analyze the long-term outcome of unselected PTCL patients treated with intensive first-line chemotherapy with high-dose therapy and ASCT. Here we report our experience with 29 patients with PTCL. The histological subtypes were as follows: peripheral T-cell lymphoma, not otherwise specified n=13; anaplastic large cell lymphoma (ALCL) ALK-negative n=5; ALCL ALK-positive n=3; ALCL with an unknown ALK status n=3; angioimmunoblastic lymphoma n=1; hepatosplenic lymphoma n=1; Sézary syndrome n=1; and enteropathy-associated T-cell lymphoma n=2. The median age at diagnosis was 48 years (29-64), most patients had advanced Ann Arbor stages (22 patients, 77%), IPI score ≥3 was found in 13 (45%) and PIT score ≥2 in 17 (59%) of the 29 patients. Eighteen patients received first-line high-dose therapy and autologous SCT consolidation; two patients were consolidaed with allogeneic SCT in the 1st complete remission and one patient in the 1st relapse. Ten patients with FDG-avid lymphoma were examined with integrated Positron emission tomography/ Computed tomography (PET/CT) at the time of diagnosis and after first-line therapy, two other patients were assessed with Positron emission tomography/ Computed tomography (PET/CT) only at time of restaging. Nineteen (66%) patients achieved complete remission, 3 (10%) partial remission and 7 (24%) patients failed the treatment. The overall response rate was 76%. PET negativity (complete metabolic response) after therapy was achieved in 8/12 (75%) individuals. After a median follow-up of 55.1 months, 14 (48.3%) patients relapsed or progressed and nine patients died (lymphoma progression). Eleven patients (50% of chemosensitive patients) survived more than 50 months. Three of the long-term survivors were treated with allogeneic SCT. The 2-year event-free survival (EFS) was 52% (95% confidence interval [CI], 0.33-0.71); the 2-year overall survival (OS) rate reached 65% (95%CI, 0.47-0.84). PET negativity was associated with a lower probability of relapse (chi-square p=0.09). Our data show that intensive first-line therapy with etoposide-doxorubicine-based regimens and ASCT consolidation may lead to long-term disease control in about a half of patients with chemosensitive PTCL. Achievement PET negativity is probably an essential prerequisite for long-term complete remission.

Frontline therapy in mantle cell lymphoma: The role of high-dose therapy and integration of new agents

Mantle cell lymphoma (MCL) is a unique lymphoma subtype comprising 6% to 8% of new lymphoma diagnoses. It is generally considered to be incurable with standard lymphoma therapies. The median overall survival (OS) is often reported to be 3 to 4 years, but more recent data suggest that the median OS may be longer than 5 years. There is considerable heterogeneity in MCL, with some patients succumbing to their disease in less than a year and others surviving for more than 10 years. The biology of MCL is reasonably well understood, and targeted therapies based on this knowledge are in development. Clinical trials incorporating new agents into standard therapies are under way. The optimal frontline treatment strategy is not defined and is a source of controversy. Intensive therapies administered to younger patients appear to produce better-quality remission than standard treatments, and one randomized clinical trial demonstrates improved OS with an intensive approach. Additional randomized clinical trials defining standard approaches are needed.

PROLONGED SURVIVAL OF PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA AFTER FIRST-LINE INTENSIVE SEQUENTIAL CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANTATION

Nodal peripheral T-cell lymphomas (PTCLs) are infrequent subtypes of non-Hodgkin's lymphomas. The WHO classification recognizes three subgroups of nodal PTCL: peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), anaplastic large cell lymphoma (ALCL) and angioimmunoblastic lymphoma (AIL). The clinical course is aggressive and despite multiagent chemotherapy, the median survival is about 2 years. Optimal first-line chemotherapy is not established and the role of high-dose therapy with autologous stem cell support is still controversial. To analyze the long-term outcome of PTCL patients treated with intensive first-line chemotherapy with highdose therapy and autologous transplant consolidation. Sequential chemotherapy protocol consisting of 3 cycles of CHOEP-21-like regimen (PACEBO), 1 cycle of an ifosfamide and methotrexate-based regimen (IVAM) and a priming regimen with high-dose cytosine arabinoside (HAM). Consolidation was provided with myeloablative conditioning (BEAM 200) and autologous stem cell support. Eighty-four patients with aggressive high-risk lymphoma were treated with the sequential protocol from 2000 to 2007 in our institution. Here we report our experience with 18 patients with nodal PTCL (10 PTCL, NOS; 3 ALCL, ALKnegative; 2 ALCL, ALK-positive; 2 ALCL, unknown ALK status; 1 AIL). Eleven (61 %) patients achieved complete remission, 3 (17 %) partial remission and 4 (22 %) patients failed the procedure. The overall response rate was 77.8 %. After a median follow-up of 25.7 months, nine patients relapsed or progressed (6 PTCL, NOS; 2 ALCL ALK-positive; 1 ALCL ALK-negative; median 14.1 months) and four patients died (lymphoma progression). The relapse was treated with allogeneic stem transplantation in one patient. The 2-year progression-free survival (PFS) was 52 % (95 % CI, 0.27 to 0.76); the 2-year overall survival rate reached 71 % (95 % CI, 0.47 to 0.95). Our results show that intensive first-line chemotherapy with high-dose therapy and autologous transplant consolidation offers a chance for long-term survival in patients with chemosensitive PTCL.

"Not only presidential candidates from Illinois" Haematology news from ASCO 2008

At the haematological sessions of ASCO 2008 major progress was reported with regard to multiple aspects of haematologic neoplasia. Highlights included the emerging role of JAK2 inhibitors in CMPD, oxametaxine as a new treatment in CML and the differential management of TKIs in refractory or relapsing CML corresponding to mutational status and comorbidities. Demethylating agents increased their share in up-to-date treatment of myelodysplasia based on the followup of several Phase III studies. In multiple myeloma the 4-year landmark analysis of the ECOGE4A03 study further questioned the role of high dose therapy and autologous transplantation compared to Lenalidomide/low dose Dexamethasone induction therapy. Multiple new therapeutic antibodies (e.g. Lumiliximab) as well as better tolerated chemotherapeutics (e.g. Bendamustin) were the cornerstone of presentations in low-grade NHL and CLL. In general the reasonable refinement of targeted therapies is coming of age.

ESMO special symposium: what is the role of high dose therapy and allografting stemcell transplantation for hematological malignancies in the era of “-nibs” and “-mabs”

ESMO special symposium: what is the role of high dose therapy and allografting stemcell transplantation for hematological malignancies in the era of “-nibs” and “-mabs”

Dose‐escalated CHOP and tailored intensification with IFE according to early response and followed by BEAM/autologous stem‐cell transplantation in poor‐risk aggressive B‐cell lymphoma: a prospective study from the GEL–TAMO Study Group

The role of high-dose therapy and autologous stem-cell transplantation (HDT/ASCT) in the up-front treatment of poor-risk aggressive lymphoma is still unknown. We conducted a prospective multi-centre trial with dose-escalated CHOP (MegaCHOP) and tailored intensification prior to HDT/ASCT according to early response assessed by CT and gallium scan (Ga67S). Eighty-six patients with newly diagnosed and Ga-67 avid aggressive B-cell lymphoma received MegaCHOP for three courses and were evaluated for response by CT and Ga67S. Patients with CT response and negative Ga67S received another MegaCHOP cycle followed by BEAM and ASCT. Those patients with positive Ga67S or without CT response received salvage treatment with two courses of ifosfamide and etoposide (IFE) followed, whenever response had been achieved, by BEAM and ASCT. Response rate before HDT/ASCT was 85% and, with 34 months of median follow-up, progression-free survival (PFS), overall survival (OS) and treatment-related mortality were 56%, 64% and 7%, respectively. For transplanted patients (81% of the whole series), PFS and OS were 67% and 74%, respectively. No different outcomes were observed between patients achieving an early negative Ga67S response treated with MegaCHOP and BEAM/ASCT and patients with mid-treatment positive Ga67S who received IFE prior BEAM/ASCT. This response-adapted strategy including early treatment modifications prior HDT/ASCT have yielded encouraging PFS and OS in patients with poor-risk B aggressive non-Hodgkin's lymphoma.

The role of high-dose therapy and stem cell rescue in the management of T-cell malignant lymphomas: a BSBMT and ABMTRR study

Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous subset of lymphomas with a poorer prognosis compared with B-cell lymphomas. We conducted a retrospective study of 82 patients who received high-dose therapy for PTCL (autologous SCT (ASCT) N=64; allogeneic SCT (Allo-SCT) N=18). With a median follow-up from ASCT of 37 months from transplant, 33 patients were alive; 20 died of progressive disease, 10 died from non-relapse mortality (NRM) with 1 unknown cause. Three-year overall survival (OS) and progression-free survival (PFS) were 53% (95% confidence interval (CI) 42, 67) and 50% (95% CI 39, 64), respectively. Factors significantly affecting OS and PFS on univariate analysis were histological subtype and chemotherapy sensitivity. In a multivariate analysis, the only factor with significant impact was chemotherapy sensitivity. After a median follow-up from Allo-SCT of 57 months, five patients were alive; five died of progressive disease and eight died from NRM. The 3-year OS and PFS were 39% (95% CI 22, 69) and 33% (95% CI 17, 64), respectively, and the 3-year relapse rate was 28% (95% CI 6, 50). These results demonstrate that high-dose chemotherapy with autologous stem cell rescue has a substantial role in the management of T-cell lymphoma. The use of full-intensity allogeneic transplantation is limited by high transplant-related mortality, and exploration of reduced intensity regimens is warranted.

Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.

Primary therapy for adults with T-cell lymphoblastic lymphoma with hematopoietic stem-cell transplantation results in favorable outcomes

Controversy exists regarding the role of high-dose therapy followed by stem-cell transplant (SCT) in the treatment of T-cell lymphoblastic lymphoma (T-LBL). We conducted an intention-to-treat analysis of the strategy of SCT as definitive treatment of T-LBL. From July 1987 to March 2005, 34 adults with T-LBL were diagnosed and treated in British Columbia. Treatment, before planned SCT, consisted of a non-Hodgkin's lymphoma (NHL)/acute lymphoblastic leukemia hybrid chemotherapy protocol (28 patients) or a standard NHL chemotherapy regimen (six patients). Median follow-up of the 23 surviving patients is 51 months (range 13-142 months). Twenty-nine proceeded to SCT (four allogeneic, 25 autologous). For all 34 patients, 4-year overall survival (OS) and event-free survival (EFS) are 72% and 68%, respectively. For patients proceeding to SCT, the 4-year OS and EFS are 79% and 73%, respectively. All patients who received allografts are alive without disease at 38-141 months since diagnosis. For patients who received autografts, the 4-year EFS is 69%. Bone marrow involvement was a significant prognostic factor predicting for a worse survival (P = 0.02). A treatment strategy for adults with chemosensitive T-LBL that includes planned consolidation with SCT in first response produces favorable long-term outcome.

Disappointing Outcomes of Peripheral T Cell Lymphoma after Autologous Stem Cell Transplantation.

The role of high dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell NHL following HDT have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Older retrospective studies found comparable survival rates after ASCT for pts with T-cell and B-cell NHL.1,2 In this study, we report our single center experience over one decade using a uniform high-dose regimen for patients with PTCL.Patients and MethodsThe transplant database of the BMT program at Cleveland Clinic was reviewed, and 32 patients undergoing ASCT for PTCL between 1996 and 2005 were identified. Twenty-one patients (66%) had anaplastic large cell lymphoma (ALCL), and 11 (34%) had peripheral T cell, not otherwise specified (PTCL-NOS). Patient characteristics are summarized in table 1.Stem cell mobilization with VP16 and GCSF priming provided a median CD34 cell dose of 5.01× 106/kg (range 2.05–29.69). Patients received a preparative regimen consisting of busulfan (either 1 mg/kg orally or 0.8mg/kg IV for 14 doses), followed by VP16 60 mg/kg IV continuous infusion, then cyclophosphamide 60mg/m2 IV daily for two days. Standard supportive care measures were employed.ResultsRecovery to 500 neutrophils/uL occurred at a median of 10 days post transplant (range 9–12 days) and platelet recovery to 20 000 at a median of 14 (range 7–60) days.Kaplan-Meier 5 year overall survival and relapse-free survival for all patients is 34% and 18%, respectively; median survival for all patients is 36 months (see figure 1). Median follow-up of 10 survivors is 25 months. No obvious plateau was observed on the overall or relapse fee survival curves. No significant difference in outcomes based on subgroup (ALCL versus PTCL-NOS) was observed. Staining for anaplastic lymphoma kinase (ALK) was available for 11 (of 21 total) anaplastic T cell lymphoma patients: 4/5 ALK-positive patients are alive compared to 2/6 ALK-negative patients at last follow-up. Four of five patients undergoing ASCT as consolidation following initial therapy are alive at a median 25 months.Based on this small patient population, and in contrast to some recent studies, our results suggest a poor outcome for patients with PTCL after ASCT. The outcome for pts undergoing ASCT in first remission, and for ALK-positive (versus ALK-negative) ALCL, requires prospective investigation.Table 1:Patient CharacteristicsCharacteristicN (%)ALCL21 (66)PTCL NOS11 (34)Male21 (66)Age: median(range)44 (16-69)2 prior chemo regimens22 (69)3 or more prior chemo regimens7 (22)Transplant in first remission5 (16)Relapsed/Refractory25 (78) [Display omitted]

The Impact of Disease Status on the Outcome of High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT) for Peripheral T-Cell Lymphoma (PTCL).

The majority of patients (pts) with PTCL present with advanced stage with high-intermediate or high-risk IPI and their prognosis are poor with current standard induction chemotherapy. HDT followed by ASCT has been shown to be effective therapy for relapsed and refractory PTCL, although the outcomes of transplant varied depending upon the histologic subtype, disease status and IPI at transplant. Given the poor outcome with current treatment approach, HDT and ASCT as consolidative therapy during first remission are being investigated in pts with PTCL. We performed retrospective analysis of all pts with T-cell, NK cell and null cell lymphomas who underwent HDT and ASCT between 2/1991 to 6/2005. We analyze the outcome based on disease status at transplant and the subset of PTCL. There were 57 pts (35 male, 22 female) with a median age of 45 years (range 5–68). Histology included 6 (10.5%) angioimmunoblastic T-cell lymphoma (AILD), 26(46%) Anaplastic large cell lymphoma (ALCL), 22 (39%) PTCL, unspecified (NOS), 1 panniculitis like T-cell, 1 NK-T, and 1 adult T-cell lymphoma. Twelve (21%) were transplanted during first remission; 11 were high intermediate-high risk IPI, and 1 for histology NK-T. Twenty-eight (49%) were transplanted during relapse or ≥second remission and 17 (30% ) induction failure or primary refractory disease. Twenty-one (37%) had advanced stage III-IV at transplant. The median number of chemotherapy regimens was 2 (range 1–5). For ALCL subtype, 9 were anaplastic lymphoma kinase (ALK) positive, 9 ALK negative, 8 unknown.Results: At a median follow-up of 22 months (range 0.5–179), 29 are alive in remission, 25 relapsed and 3 died from transplant related mortality. One patient developed therapy induced myelodysplasia at two years post ASCT and is alive in remission after allogeneic stem cell transplant. The 2 years overall survival (OS) and disease-free survival (DFS) for the whole group were 53% (95% CI 46–60), and 45% (95% CI 39–50), respectively. The OS and DFS were significantly better for pts. who were transplanted in first complete remission (Figure1). The 2-year OS and DFS were both 83% (95% CI 55–94) for pts. transplanted in first remission compared to 45% (95% CI 38–52%, p=0.03) and 35% (95% CI 30–40, p= 0.006), respectively for those transplanted beyond first remission. Univariate models showed that the risk of death and/or relapse was significantly less among the pts. transplanted in first complete remission (OS, DFS and time to relapse: p < 0.05). When compared the outcome among the 3 subtypes, AILD, ALCL and PTCL NOS, there were no significant differences in survival or relapse among the 3 groups.Conclusion: our results suggest that HDT and ASCT can improve prognosis and survival of pts. with PTCL. The outcome of ASCT is best when performed during first complete remission. The role of HDT and ASCT during first remission should be further investigated in larger multi-center studies. In contrast to other reports, the prognosis of pts. with ALCL is similar to other PTCLs. [Display omitted]

The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas

The prognosis for children with bone and soft tissue sarcomas has significantly improved since the advent of effective multiagent chemotherapy, aggressive surgery for local disease and more precise delivery of radiotherapy doses. However, in a small proportion of patients that present with high-risk disease, long-term outcome has not substantially increased, with disease-free survival rates still in the order of 20–30%. It is therefore clear that novel therapies are needed for children with these tumors. Based on the highly chemosensitive nature of the majority of pediatric sarcomas, several small studies have been conducted to investigate the potential role of high-dose chemotherapy followed by hematopoietic stem cell reconstitution. This review will provide an overview of the current literature concerning the use of high-dose therapy with stem cell transplantation for the three main pediatric sarcomas – Ewing sarcoma, rhabdomyosarcoma and osteosarcoma.

The role of high-dose therapy and autologous stem cell transplantation in patients with primary refractory Hodgkin's lymphoma: a report from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

GISL recently conducted an exhaustive survey of 1078 patients with Hodgkin's Lymphoma (HL) enrolled between 1988 and 2002 in different prospective trials. Treatment failure was observed in 82 out of 1078 patients; of these 82 patients with refractory HL, complete information was available for 72, who form the evaluable population of the present study. After the initial therapy failure, 51 patients were treated with conventional salvage chemotherapy (CC) (n = 24) or high-dose chemotherapy (HDC) (n = 27); 4-year overall survival (OS) was 81% in the HDC group versus 38% in the CC group (P = 0.019). The remaining 21 patients had rapidly progressive disease and died. After a median follow-up of 2.8 years, the projected OS for all 72 patients is 58 and 49% at 3 and 5 years, respectively. Age <45 years, the absence of systemic symptoms and a PS <1 predicted a significantly longer OS. Interestingly, the majority of patients with two or three negative prognostic factors did not receive potentially curative therapy. In conclusion, HDC seems to be a reasonable option for selected patients with refractory HL, although the majority of them did not receive a transplant. Finally, patients with a high-risk score had little chance of receiving potentially curative treatment.

The Role of High Dose Therapy and Stem Cell Rescue in the Management of T-Cell Malignant Lymphomas (TCL): A BSBMT and ABMTRR Study.

Malignant lymphoma of a T-cell phenotype (TCL) account for only 15% of lymphomas in Europe/North America and associated with a poorer prognosis compared with B-cell phenotype lymphomas. Whilst cumulative experience has shown that high dose chemotherapy and autologous stem cell rescue (ASCT) is an effective salvage therapy in B-cell disease the role of ASCT and especially full intensity Allogeneic stem cell transplantation (HSCT) in T-cell disease, is limited. This study represents a collaborative retrospective case analysis of patients undergoing ASCT/HSCT for T-cell lymphoma. The aim of the study was to determine the impact of ASCT/HSCT on disease responsiveness, treatment-related toxicities and to examine influencing factors in relation to outcomes. All recipients of ASCT and HSCT performed in 1990 through 2002 for PTCL and reported to the British Society of Bone Marrow Transplantation (BSBMT) and the Australian Bone Marrow Transplant Recipient Registry (ABMTRR) were eligible for the study and data was examined retrospectively using a structured data retrieval proforma. Eighty-three patients received high dose therapy for TCL (ASCT n=65, HSCT n=18) with a median age of 28 years (12–52 yrs) in the HSCT group and 45 years (17–70 yrs) in the ASCT group, p<0.0001. Histological categorisation was heterogeneous with 30/65 patients (42%) in the ASCT group and 9/18 patients (32%) in the HSCT group being TCL-NOS, p<0.0001. The median number of therapies prior to ASCT and HSCT were similar (2, range 1–7) including 2 patients in the HSCT group who had received a prior ASCT. Disease status at transplant was: CR1 (ASCT 48%, HSCT 33%), CR2 (ASCT 6%, HSCT 6%), PR (ASCT 23%, HSCT 44%) and progressive disease (ASCT 22%, HSCT 17%). 54% of patients in the ASCT group received BEAM conditioning and 67% of the HSCT group received TBI-based regimen supported by matched-related (13/18), matched-unrelated (4/18) haplo-identical (1/18) grafts. With a median follow-up from ASCT of 18.3 months (range 1–100 months) 34 patients were alive; 21 died of progressive disease, 4 died from sepsis and 5 died from pneumonia. With a median follow-up from HSCT of 30 months (range 1–89 months), 5 patients were alive; 5 died of progressive disease, 3 died of acute GvHD (6/18 experienced grade II-IV acute GvHD), 4 died from sepsis and 1died from a secondary malignancy. The 5 yr OS is 45% in the ASCT group and 29% in the HSCT group (p=0.06) and the 5 yr PFS is 42% in the ASCT group and 22% in the HSCT group (p=NS). The 5 yr relapse rates were 32% and 28% (p=NS) in the ASCT and HSCT groups, respectively with a higher non-relapse mortality (NRM) in the HSCT group compared with the ASCT group (50% vs 23%, p=0.024). In a multi-variate analysis, the only factor to significantly impact both OS and PFS was chemosensitive disease (p=0.015 & p>0.01, respectively). These results suggest that ASCT has a significant role in the management of TCL, though full intensity HSCT is limited by both high NRM and limited evidence of graft-versus-lymphoma effect. Further exploration of reduced intensity HSCT may help to establish a role for HSCT in the management of TCL.

Durable remissions are rare following high dose therapy with autologous stem cell transplantation for adults with "paediatric" bone and soft tissue sarcomas.

BackgroundThe role of high dose therapy (HDT) with autologous stem cell transplantation (AuSCT) for the treatment of bone and soft tissue sarcomas remains investigational. There are few reports examining this strategy focusing on the adult population.MethodsWe retrospectively reviewed our experience of adult patients undergoing HDT and AuSCT for 'paediatric' sarcomas.ResultsA total of 17 patients (14 male, 3 female) with median age at transplant of 24 years (range 20 – 41) were identified. The diagnosis was Ewings sarcoma/PNET (10), osteosarcoma (5) and rhabdomyosarcoma (2). Status prior to HDT, following conventional-dose chemotherapy +/- surgery +/- radiotherapy, was complete remission (CR) (6), partial remission (PR) (6), stable disease (1) and progressive disease (4). There was no transplant-related mortality. Two patients remain disease free beyond four years and both received HDT as part of their primary therapy (CR1 and PR1) however, the median progression free survival and overall survival following AuSCT for the entire cohort was only 7 months (range: 2–92 months) and 13 months (range: 2 – 92 months), respectively.ConclusionHDT and AuSCT infrequently achieves prolonged remissions in adult patients and should only be considered in patients who are in a PR or CR following conventional-dose therapy. Further studies are required to define the role of HDT with AuSCT for adult patients with sarcoma.

Liver transplantation for HBV and management of reinfection

Follicular non-Hodgkin's lymphoma (NHL) represents the most common indolent lymphoma with a median survival of 10 years. A new prognostic index (FLIPI) provides prognostic information at diagnosis and at relapse. Initial treatments combining monoclonal antibody therapy using rituximab with chemotherapy appear to increase the response rate and decrease the risk of relapse with little increase in toxicity. Promising phase III trial results demonstrating improvements in outcome using rituximab have recently been reported. A number of phase II trials have also demonstrated encouraging activity combining radiolabeled antibodies in sequence with chemotherapy. The role of high-dose therapy and autologous transplantation is becoming more defined, with improvements in progression-free survival observed in the upfront and relapsed setting. The application of allogeneic transplantation, once restricted to young otherwise healthy patients has shown encouraging activity in older, relapsed, and refractory patients using nonmyeloablative conditioning regimens. These new treatment options make the management of newly diagnosed patients both exciting and a challenge.

Patients with Lymphoplasmacytic Lymphoma Can Be Salvaged with Autologous Stem Cell Transplantation, Irrespectively of the Number of Previous Treatment Lines. Analysis of 146 Cases from the European Bone Marrow Transplant Registry (EBMT).

Lymphoplasmacytic Lymphoma (LPL) is a relatively rare low-grade lymphoma which primarily affects elderly patients. Standard doses of alkylating agents, purine analogues and anti-CD20 monoclonal antibody effect response rates of up to 60%. However, complete response is infrequent and there is no cure. Due to indolent nature of the disease and older patients with comorbidities, evaluation of the role of high dose therapy with transplant has been infrequent in the past. Here we report a retrospective multicentre study of 146 LPL patients (94 male, 52 female), who underwent autologous stem cell transplantation (ASCT) between 1992 and 2004.The median age was 60 years (54–67) and median time from diagnosis to transplant was 62 months (5–119). Twenty-six patients (18%) were in CR1, 35 (24%) in CR2, 30 (20%) in ≥CR3, 45 (31%) in PR, 10 (7%) primary refractory at transplant. Combination of GCSF with either Cyclophosphamide, ESHAP or AraC were mainly the stem cell mobilisation regimens used, and 18 patients with extensive prior use of purine analogues, required second attempt for harvesting. The conditioning regimens used were BEAM, Cyclophosphamide/TBI or Melphalan/TBI. The source of stem cells was PBSC in 129, BM in 11 and both in 6 patients. All patients except one had successful engraftment. With a median follow-up of 12 months (2–126), 131 (90%) patients are alive and 15 (10%) dead. Thirteen patients died from disease progression and 2 from regimen toxicity. Actuarial non- relapse mortality was 2.4% at 1 and 2 years. The actuarial OS was 90% at 1 year, 79% at 3 years and 69% at 5 years. The probability of relapse was 80% at 1 year, 53% at 3 years and 39% at 5 years. Relapse rate was not statistically significant for patients with chemosensitive disease. In conclusion this study shows that ASCT is safe, and a significant proportion of previously multitreated LPL patients can be salvaged and sustain prolonged DFS.

High Dose Therapy with Autologous Blood Stem Cell Transplantation (ASCT) for Follicular Lymphoma: Long-Term Outcome According to Histologic Grade.

Follicular lymphoma is generally an indolent disease with a relatively long natural history requiring multiple therapies over many years. The optimal combination and sequence of these therapies continue to evolve. Despite substantial supporting evidence (including a recently published, randomized study), the role of high dose therapy with ASCT in follicular lymphoma has been questioned. Therefore, we reviewed the Cleveland Clinic experience to determine the long-term outcome of follicular lymphoma patients according to histologic grade. Between June 1991 and June 2004, 105 patients with relapsed, grade 1–3, follicular lymphoma (without histologic transformation) received high dose CBV (n=9) or BuCyVP (n=96) and ASCT at the Cleveland Clinic. The median follow-up among survivors is 4.4 (0.1–11.4) years.Table of patient, disease, ASCT characteristics, and outcomeVariableGrade 1 (n=45)Grade 2 (n=36)Grade 3 (n=24)p-valueAge: median (range)49(35–62)51(33–58)53(42–64)0.042Male sex: N (%)23(51)20(56)12(50)0.89Years from diagnosis to ASCT: median (range)3.0(0.4–15.7)3.0(0.9–17.6)2.3(0.6–15.2)0.34Prior # chemotherapy regimens: 2–3/>4, N (%)36(80)/9(20)32(89)/4(11)19(79)/5(21)0.49Disease status at ASCT: CR/PR, N (%)6(13)/33(73)10(28)/22(61)6(25)/15(63)0.58Bone marrow status at ASCT: +/−, N (%)8(23)/27(77)4(13)/28(88)4(18)/18(82)0.54Prior radiation therapy: N (%)14(31)11(31)5(21)0.63LDH > normal at ASCT: N (%)28(62)27(77)13(54)0.16Tumor bulk >10 cm at ASCT: N (%)8(18)6(17)5(21)0.92Disease progression: N (%)20(44)13(36)11(46)–Death: N (%)17(38)11(31)10(42)–Kaplan-Meier freedom from progression and overall survival according to histologic grade are shown: [Display omitted] By Cox proportional univariate analysis, male sex, ≥4 prior chemotherapy regimens, and elevated LDH predicted a higher risk of progression while prior radiation therapy and bone marrow involvement predicted a higher risk of death. By Cox proportional multivariate analysis, male sex and elevated LDH predicted a higher risk of progression while prior radiation therapy and tumor bulk predicted a higher risk of death. In conclusion, approximately half of all patients that receive high dose therapy and ASCT for relapsed follicular lymphoma of any histologic grade enjoy long-term remissions and survival. ASCT remains one of the most beneficial treatment options for many patients with relapsed follicular lymphoma.

An update on the role of high-dose therapy with autologous or allogeneic stem cell transplantation in mantle cell lymphoma.

Early trials of high-dose therapy with autologous stem cell transplantation in mantle cell lymphoma were discouraging, with no clear survival advantage attributable to the procedure. Most early series were plagued by small numbers, retrospective designs, and short follow-up. Also, until recently, allogeneic stem cell transplantation was not an option for most mantle cell lymphoma patients who were too old or infirm to tolerate standard conditioning regimens. New advances in allogeneic transplantation, particularly reduced-intensity conditioning regimens, have increased the availability of this procedure to patients with mantle cell lymphoma. New evidence has emerged during the last several years that suggests autologous stem cell transplantation in first complete remission may provide a survival advantage over conventional chemotherapy in patients with mantle cell lymphoma. Additionally, investigational strategies such as in vivo purging with rituximab and the use of radioimmunotherapy in conditioning regimens may further increase response rates and, hopefully, survival in mantle cell lymphoma patients. Finally, recent studies suggest the existence of a graft-versus-lymphoma effect in mantle cell lymphoma providing strong scientific rationale for the possible curative potential of allogeneic stem cell transplantation in this disease. This review focuses on recent advances in allogeneic and autologous transplantation for mantle cell lymphoma. Particular emphasis is placed on the role of autologous transplantation in first complete remission, the role of in vivo purging with rituximab, the utility of radioimmunotherapy and, finally, the evolving strategy of reduced-intensity allogeneic stem cell transplantation.

The role of stem cell transplantation in the treatment of follicular lymphoma

Follicular lymphoma (FL) is highly sensitive to chemo- and radiotherapy. However, cure can not be achieved with conventional chemotherapy. Results from several large clinical trials indicate that 50–60% of patients treated with high dose chemo-/radiotherapy (HDT) and autologous blood stem cell transplantation (SCT) for relapse after standard chemotherapy have a 3–5-year chance of disease-free survival (DFS). Overall as well as disease-free survival are improved in patients with negative results in sensitive PCR assays for the disease-specific t(14;18) translocation in bone marrow (BM) or peripheral blood samples taken after transplantation. These data compare favourably to historical results with standard dose chemotherapy. The role of high dose therapy and autologous stem cell transplantation in the primary treatment of follicular lymphoma is presently addressed in randomized trials. Patients with refractory disease or relapsing from standard as well as high dose therapy can achieve long term complete remissions (CR) with allogeneic blood stem transplantation mainly due to the graft-versus-lymphoma effect of the donor immune system.