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Biomedical subjects

R Champlin

Publications and source records attributed to R Champlin.

At least 19 recordsLinked to original sources
PubMed2003

Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation: feasibility and results.

We conducted a retrospective analysis of all allogeneic stem cell transplantation (ASCT) patients started on extracorporeal photopheresis (ECP) for the management of steroid-dependent (SD) or steroid-refractory (SR) cutaneous chronic graft-versus-host disease (cGVHD) following ASCT during a 36-month period (9/98-8/01). Only SD or SR patients who were treated by ECP after day 100 and who received at least 4 weeks of ECP were considered evaluable for this analysis. Out of 64 ASCT patients reviewed, 32 patients met the inclusion criteria. All 32 patients had been previously treated with systemic corticosteroids with 11 (34%) being SR and 21 (66%) SD. Cutaneous cGVHD was extensive in 28 patients (88%) and was accompanied by visceral (hepatic, gastrointestinal) cGVHD in 23 patients (72%). The 32 evaluated patients had received a median of three prior therapies before ECP, most commonly systemic corticosteroids, tacrolimus, and mycophenolate mofetil. Patients received a median of 36 ECP sessions (range 12-98) over a median of 5.3 months (range 1-28), with a median of six sessions per month. The complete response (CR) rate was 22% (n=7) and the partial response rate was 34% (n=11). In all, 28 patients were on systemic corticosteroid therapy at ECP initiation and 18 patients achieved 50% dose reduction while on ECP, yielding a 64% steroid-sparing response rate. Of seven CRs, five are ongoing. A total of 11 (34%) patients have died after ECP, with all cases due to visceral cGVHD or cGVHD-related infectious complications. All 21 surviving patients remain on at least some immunosuppressive cGVHD therapy (including ECP in eight). Overall, ECP displays a substantial response rate and, in particular, steroid-sparing activity in SR/SD extensive cutaneous cGVHD. However, most patients continue to require at least some chronic therapy and cGVHD-related morbidity and mortality remain high.

Adolescent↗
PubMed2003

Adult stem cells and tissue repair.

Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells.

Adult↗
PubMed2002

Fludarabine/melphalan conditioning for allogeneic transplantation in patients with multiple myeloma.

The purpose of the study was to determine the feasibility and efficacy of a reduced intensity conditioning regimen of fludarabine and melphalan for allogeneic transplantation in patients with multiple myeloma. From August 1996 to December 2000, 22 patients received a reduced intensity conditioning regimen with fludarabine and melphalan. Median age was 51 years (range, 45-64), median time from initial therapy to transplant was 36 months (range, 3-135 months). Disease phase prior to transplant was primary refractory in two patients, refractory relapse in 11 patients, sensitive relapse in eight patients and initial remission consolidation in one patient. The median number of prior therapies was five (range, 1-7), and median beta 2 microglobulin prior to transplant was 3.0 mg/l (range, 1.0-7.3). All patients received unmanipulated grafts from either HLA matched sibling donors (n = 13) or matched unrelated donors (n = 9). Eighteen patients received fludarabine 30 mg/m(2) for 4 days with melphalan 140 mg/m(2) as a single dose and four patients received fludarabine 25 mg/m(2) for 5 days with melphalan 90 mg/m(2) daily for 2 days. All 21 patients evaluable for engraftment achieved a neutrophil count of >0.5 x 10(9)/l after a median of 12 days (range, 9-24), 18 patients achieved platelet transfusion independence after a median of 14 days (range, 8-47). All engrafting patients had 100% donor cell engraftment. Seven patients achieved a complete remission. Six patients are currently alive with a median follow-up of 15 months (range, 10-47 months). The actuarial survival and progression-free survival is 30 +/- 11% and 19 +/- 9% at 2 years. Non-relapse mortality at 100 days was 19 +/- 10% and 40 +/- 10% at 1 year. Fludarabine/melphalan combinations are feasible and allow consistent engraftment of allogeneic progenitor cells from both related and unrelated donors in patients with multiple myeloma and should be explored in patients with less advanced disease.

Antineoplastic Agents↗
PubMed2002

Chronic graft-versus-host disease manifesting as polymyositis: an uncommon presentation.

Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation. Polymyositis can occur in association with chronic GVHD and mimics the idiopathic form of the disease. We report two cases of chronic GVHD-associated polymyositis and review the published literature. The two patients presented 13 and 19 months after allogeneic transplantation with characteristic features of muscular hypotrophy, proximal muscle weakness, pain, elevated creatine phosphokinase (CPK), aldolase and SGPT. Interestingly, both patients had HLA DR52 genes, which is frequently reported in association with idiopathic polymyositis. Electromyogram (EMG) and muscle biopsy confirmed the diagnosis. Treatment with cyclosporine or tacrolimus resulted in complete and sustained remission of polymyositis in both cases. A review of the literature shows cyclosporine and steroids are well-described treatment options for patients with myositis in post transplant, as well as idiopathic cases. The duration of immunosuppressive treatment has varied in different reports, and there is a risk of recurrence when immunosuppression is tapered.

Adult↗
PubMed2002

Comparison of competitive-nested PCR and real-time PCR in detecting BCR-ABL fusion transcripts in chronic myeloid leukemia patients.

Real-time RT-PCR has great advantages for estimating transcript levels in a variety of situations. These include relative rapid assay times (hours), reliability and ease of performing replicate analyses. In contrast, competitive PCR is a very labor-intensive procedure requiring a few days to generate useful data. We compared the same samples from CML patients by both methods. Importantly, we used the Bcr-Abl junction plasmid DNA, which is used as a competitor in the manual competitive PCR assay, to generate a standard curve for the real-time assay. This permitted reporting the real-time data as the number of BCR-ABL transcripts per microg of total RNA, which is the same format used for the competitive PCR assay. In this study, a total of 435 peripheral blood and marrow samples from 285 CML patients were analyzed by RT-PCR; these patients were undergoing therapy by STI-571, interferon, and bone marrow transplantation treatment. Most samples also had assay values for the Philadelphia chromosome (Ph), FISH and Western blotting for the Bcr-Abl oncoprotein. Our findings indicated that the real-time assay was less sensitive than the manual competitive RT-PCR assay (t = 5.118; P < 0.001). Of interest, the transcript levels in cell line mixtures with various ratios of K562/KG-1 (BCR-ABL positive/negative) cells were also significantly higher with the competitive RT-PCR assays than real-time RT-PCR, except for levels of BCR-ABL below 200 transcripts per microg of RNA. In both patient and cell line experiments, dividing the BCR-ABL transcripts by the total ABL transcripts virtually eliminated the difference between real-time BCR-ABL transcript values and quantitative competitive BCR-ABL transcript values, indicating that both BCR-ABL and ABL transcripts were underestimated by the real-time assay. In addition, the increased sensitivity of the nested, competitive RT-PCR was readily apparent in patients with minimal residual disease, which by the real-time were negative in the majority of patients but were positive by nested, competitive RT-PCR in 44.6% (n = 29) of samples analyzed (n = 65). These findings indicate that real-time RT-PCR, when normalized for the total ABL transcripts, can be used to monitor CML patients during therapy, but we suggest that nested, competitive RT-PCR be used to determine BCR-ABL/ABL transcript ratios at low transcript values or especially when real-time analyses are negative.

Fusion Proteins, bcr-abl↗
PubMed2001

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation.

The incidence, characteristics, risk factors for, and impact of chronic graft-vs-host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA-identical blood stem cell transplant recipients. Minimum follow-up was 18 months. Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of corticosteroids on day 100, and total nucleated cell dose were significant risk factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD prophylaxis with tacrolimus and methotrexate was associated with a reduced risk of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease status at the time of transplantation, high-risk chronic GVHD had an adverse impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P <.001) at 18 months. It was concluded that there is a substantial rate of chronic GVHD after HLA-identical allogeneic blood stem cell transplantation, that clinical factors may alter the risk of chronic GVHD, and that high-risk chronic GVHD adversely affects outcome.

Adolescent↗
PubMed2001

Controlled trial of filgrastim for acceleration of neutrophil recovery after allogeneic blood stem cell transplantation from human leukocyte antigen-matched related donors.

The rapid recovery of hematopoiesis after allogeneic blood stem cell transplantation has been attributed to the quality and quantity of hematopoietic progenitors in the blood stem cell grafts from filgrastim-stimulated donors. To determine whether further stimulation with filgrastim after transplantation would affect hematopoietic recovery, a prospective, randomized, controlled study was performed. Forty-two adult recipients of allogeneic blood stem cells from human leukocyte antigen-matched related donors were randomized to receive 10 microg/kg per day filgrastim subcutaneously from day 1 through neutrophil recovery or no growth factor support after transplantation. There was no significant difference between the 2 groups in the number of CD34(+) cells infused (median, 4.8 vs 4.3 x 10(6)/kg). Graft-versus-host (GVHD) disease prophylaxis consisted of tacrolimus and steroids for 9 patients and tacrolimus and minimethotrexate for 33 patients. The group receiving filgrastim had a shorter time to neutrophil levels greater than 0.5 x 10(9)/L (day 12 vs day 15, P =.002) and to neutrophil levels greater than 1.0 x 10(9)/L (day 12 vs day 16, P =.01). The filgrastim group also had a trend for earlier discharge (day 16 vs 20, P =.05). There was no significant difference between the groups in time to platelet recovery, number of transfusions, regimen-related toxicity, infection, incidence of GVHD, relapse, survival, or hospital charges. It can be concluded that the administration of filgrastim after allogeneic blood stem cell transplantation shortens the time to neutrophil recovery. (Blood. 2001;97:3405-3410)

Adolescent↗
PubMed2001

Preemptive control of graft-versus-host disease in a murine allogeneic transplant model using retrovirally transduced murine suicidal lymphocytes.

Suicidal lymphocytes could greatly expand the role of allogeneic transplantation by reducing graft-versus-host disease (GVHD) as a barrier to transplantation, but optimization of their use is hindered by the lack of adequate animal models. To develop an animal model that used retrovirally transduced suicidal lymphocytes in a GVHD setting, a well-characterized MHC-matched murine transplant model (B10.BR-->AKR/J) was adapted. B10.BR splenic lymphocytes stimulated with concanavalin A and interleukin 2 were infected with a retrovirus containing the low-affinity nerve growth factor receptor (LNGFR) and the HSV-TK gene and immunomagnetically selected; these LNGFR+/TK+ allogeneic lymphocytes were then cotransplanted with 1 x 10(7) bone marrow cells into lethally irradiated AKR/J recipients. The LNGFR+/TK+ donor lymphocytes persisted in the peripheral circulation for 6 months in both syngeneic and allogeneic settings. Doses of 2 x 10(6) TK+ allogeneic lymphocytes produced GVHD with a severity and time course similar to that induced by naive lymphocytes. Survival of TK+ allogeneic lymphocyte-bearing mice was significantly improved (P = 0.01) when ganciclovir (GCV; 2 mg/day) was administered on days 7-13 post transplant by i.p. injection, demonstrating that GVHD could be prevented. Fluorescence-activated cell sorting analysis demonstrated 4-fold reduction but persistent circulation of LNGFR+ lymphocytes in mice treated with GCV at various time points 1-3 months after transplantation, demonstrating selective killing of GVHD-reactive cells. We conclude that retrovirally transduced LNGFR+/TK+ murine lymphocytes can be produced, persist after transplant, remain alloreactive, and can be killed by GCV administration, resulting in reduced GVHD.

Animals↗
PubMed2001

Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.

A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m(2) daily for 5 days in combination with melphalan 180 mg/m(2) (n = 66) or 140 mg/m(2) (n = 12). Eight patients received cladribine 12 mg/m(2) continuous infusion for 5 days with melphalan 180 mg/m(2). The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Nonrelapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95% CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control can be achieved with reduced-intensity conditioning in this population.

Acute Disease↗
PubMed2001

Expression of a truncated first exon BCR sequence in chronic myelogenous leukemia cells blocks cell growth and induces cell death.

We have shown that a deletion mutant form of Bcr [Bcr(64-413)] is a strong inhibitor of the tyrosine kinase of Bcr-Abl in vitro and also inhibits its oncogenic growth effects (Liu et al., Cancer Res., 56: 5120-5124, 1996). To determine the effects of this Bcr-Abl kinase inhibitor on chronic myelogenous leukemia (CML) cells, we cloned BCR(64-413) into a recombinant, replication-defective adenovirus to express useful quantities of Bcr(64-413) in a wide variety of cells in culture. Infection of Cos1 cells with plaque-purified virus at a multiplicity of infection of 20-40 induced high expression of Bcr(64-413) as detected by Western blotting. Infection of hematopoietic cells at modest multiplicities of infection (20-40) required special conditions involving shifting cycling cells to a nongrowing condition involving serum starvation and cell crowding. Under these conditions, both Bcr-Abl-positive and -negative hematopoietic cells can be efficiently infected by adenovirus, as demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of cells infected by beta-galactosidase (beta-GAL) adenovirus. We found that expression of Bcr(64-413) in Bcr-Abl-positive K562 and BV-173 cells, but not Bcr-Abl-negative SMS-SB cells, increased cell-cell clumping and inhibited cell growth. In contrast to the effects of the Bcr(64-413) adenovirus, the beta-GAL adenovirus, despite infecting both types of cells, did not block growth or increase cell-cell clumping of Bcr-Abl-positive and -negative hematopoietic cells. Expression of Bcr(64-413) protein in primary cultures of cells from CML patients with active disease interfered with cell growth, induced apoptosis (as measured by annexin staining), and increased cell-cell clumping, whereas the beta-GAL adenovirus and mock-infected cells lacked these effects. In contrast, normal marrow cells did not exhibit these effects on infection with Bcr(64-413) adenovirus. We conclude from these findings that Bcr(64-413) interferes with the oncogenic effects of Bcr-Abl and therefore has the potential for use in therapy of CML.

Adenoviridae↗
PubMed2001

Orbital mass secondary to precursor T-cell acute lymphoblastic leukemia: a rare presentation.

We describe a 40-year-old woman with a history of precursor T-cell acute lymphoblastic leukemia who developed an orbital mass associated with diffuse infiltration of the paranasal sinuses. The clinical and radiologic findings suggested an orbital abscess. Examination of orbital and ethmoid sinus biopsy specimens revealed relapse of precursor T-cell acute lymphoblastic leukemia. Although orbital involvement by granulocytic sarcoma (also known as extramedullary myeloid cell tumor and chloroma) with or without concurrent acute myeloid leukemia is well described in the literature, similar presence of acute lymphoblastic leukemia of either precursor T-cell or B-cell lineage is rare.

Adult↗
PubMed2001

Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia.

Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA-matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95% CI, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0.02). Three-year survival was 26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% transplanted for AML in relapse, and 17% with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients.

Adolescent↗
PubMed2001

Donor lymphocyte apheresis for adoptive immunotherapy compared with blood stem cell apheresis.

Donor lymphocyte transfusion has gained considerable interest as adoptive cellular immunotherapy for prevention or treatment of relapse after allogeneic stem cell transplantation. This study was designed to compare the yield of CD3(+), CD3(+)4(+), CD3(+)8(+), CD19(+), CD3(-)56(+)16(+), and CD34(+) cells contained in apheresis products from 61 consecutive non-cytokine treated, human leukocyte antigen (HLA)-matched donors for lymphocyte collection with the corresponding apheresis-derived cell yield from 112 consecutive, HLA-matched donors for blood stem cell collection who received recombinant human granulocyte colony stimulating factor (rhG-CSF, filgrastim) 6 microg/kg every 12 hours until cell collection was completed. Apheresis was started on day 4 or 5 of rhG-CSF treatment. The yield of lymphoid subsets was significantly different in the two sample groups, rhG-CSF treated product yields exceeding untreated product yields by a median of 2.1-fold (range: 1.3-2.6). However, the CD34(+) cell yield in rhG-CSF-treated apheresis products exceeded untreated products by 26-fold. A single untreated apheresis procedure was usually sufficient to collect a target dose of 1 x 10(8)/kg CD3(+) cells. Untreated apheresis products contained a median of 0.2 x 10(6)/kg CD34(+) cells. A potential engraftment dose of > or =0.5 x 10(6) CD34(+) cells per kg of recipient body weight was contained in 16% of 57 untreated apheresis products. One single apheresis performed in a normal, untreated donor provides a sufficient amount of CD3(+) cells for adoptive immunotherapy. Compared with that of an rhG-CSF stimulated apheresis product, the CD34(+) cell count is usually, but not always, below the engraftment dose range. RhG-CSF treatment has little effect on the yield of lymphoid subsets collected by apheresis but is highly selective of the release of CD34(+) cells. This report provides baseline data for studies that will show whether other cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF) and/or Flt-3 Ligand can immunomodulate allotransfusates in vivo to improve the graft-vs.-leukemia (GVL) effect after allogeneic stem cell transplantation, while lowering the incidence and severity of graft-vs.-host disease (GVHD).

Adult↗
PubMed2001

Long-Term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation.

Donor lymphocyte infusions (DLIs) are an effective treatment for relapsed Chronic myeloid leukemia (CML) after allogeneic transplantation but are limited by the occurrence of GVHD. CD8+ T lymphocytes are involved in the pathogenesis of GVHD but may not be essential for the graft-versus-leukemia (GVL) effect in CML. We have treated 26 CML patients with posttransplantation relapse with CD8-depleted DLI. Thirteen of 15 patients (87%) who relapsed in early-phase CML achieved complete cytogenetic response, but only 1 of 11 who relapsed in advanced-phase disease achieved complete response. Acute GVHD occurred in 2 patients (8%), and extensive chronic GVHD occurred in 2 patients (11%). Treatment-related mortality was 11.5%. Responses were durable; with a median follow-up of 4.2 years (1-7.5 years), only 1 responding patient relapsed (7%). CD8-depleted DLI was equally effective and safe after unrelated donor transplants and sibling transplants. Cytogenetic clonal evolution at the time of DLI was not predictive of treatment failure unless associated with hematologic criteria for disease acceleration. CD8 depletion is an effective method to separate GVL from GVHD for posttransplantation relapsed CML. This strategy is associated with durable complete remissions and a low rate of complications and therefore merits further investigation in larger-scale comparative trials.

Adult↗
PubMed2001

Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival.

The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m(2) and etoposide 900 mg/m(2) with G-CSF 5 microg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m(2), mitoxantrone 20 mg/m(2) and G-CSF 5 microg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m(2), etoposide 1200 mg/m(2) and cisplatin 135 mg/m(2) with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24-61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% +/- 12% after two cycles and the complete response rate was 41% +/- 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC <0.5 x 10(9)/l was 6 days (range 3-12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% +/- 14% and survival is 52% +/- 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used.

Adolescent↗
PubMed2001

Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation.

Allogeneic hematopoietic transplantation is an effective therapy for a range of malignancies. High doses of myelosuppressive chemotherapy or radiation have been used in preparative regimens with the goal of preventing graft rejection and eradicating malignancy. Much of the benefit of transplantation, however, results from graft-versus-malignancy effects, mediated by donor immunocompetent cells. An alternative approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow graft-versus-malignancy effects to develop. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly or medically infirm patients not eligible for myeloablative therapy. Nonmyeloablative preparative regimens appear promising in diagnoses sensitive to graft-versus-malignancy effects and provide a platform for further development of cellular immunotherapy. Controlled clinical trials are warranted to define the role of nonmyeloablative allogeneic transplants in a range of hematologic malignancies and selected solid tumors.

Graft vs Tumor Effect↗
PubMed2001

Thiotepa, busulfan, cyclophosphamide (TBC) and autologous hematopoietic transplantation: an intensive regimen for the treatment of multiple myeloma.

The study was designed to evaluate the efficacy and safety of an intensive, tri-alkylator conditioning regimen, consisting of thiotepa, busulfan and cyclophosphamide (TBC), prior to autologous hematopoietic cell transplantation in patients with multiple myeloma (MM) and to analyze factors associated with outcome. One hundred and twenty patients with MM received high-dose chemotherapy with TBC followed by autologous bone marrow (n = 24) or peripheral blood stem cell (PBSC) transplantation (n = 96). Fifty-four patients had chemosensitive disease and 66 had refractory disease at the time of transplantation. The overall response rate was 81% and the complete remission (CR) rate was 26%. Patients with chemosensitive disease had a CR rate of 52% vs 5% for patients with refractory disease. Multivariable analysis determined disease status at transplant as the factor most likely associated with long survival. Estimated median survival was 48, 35 and 9 months for patients with chemosensitive, primary refractory or disease in refractory relapse, respectively. Short interval from diagnosis to transplant among patients with primary refractory disease and younger age were also favorable prognostic factors for survival. Patients with refractory disease pre-transplant who achieved remission criteria rapidly after treatment had a worse outcome than the slow responders. Treatment-related mortality with the introduction of PBSC and better supportive care was 4.8%. In conclusion, TBC is an effective and relatively well-tolerated intensive conditioning regimen in patients with MM. A more favorable outcome was observed in patients with chemosensitive disease and with early treatment for primary refractory disease. TBC merits further study in these subgroups and comparison with alternative regimens in prospective studies is warranted.

Adult↗