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Autologous Stem Cell Transplantation (autologous + stem_cell_transplantation)
Selected AbstractsConsensus guidelines for ,rainy day' autologous stem cell harvests in New South WalesINTERNAL MEDICINE JOURNAL, Issue 4 2008J. Trotman Abstract Autologous stem cell transplantation (ASCT) has a well-established role in the treatment of haematological malignancies. Stem cells are commonly collected following salvage chemotherapy although there may be advantages in collecting earlier in the disease course. A 'rainy day' harvest (RDH) refers to the collection of autologous haemopoietic stem cells for long-term storage. Although there are few data to support RDH, there is increasing evidence that such harvests are being carried out, creating storage pressures in stem cell laboratories across New South Wales. The Bone Marrow Transplant Network New South Wales conducted a three-staged exercise to develop consensus-based RDH guidelines. Using available evidence, guidelines were developed supporting RDH for specific patients with acute and chronic myeloid leukaemias, follicular and other lymphomas, and multiple myeloma. Physician agreement with these disease-specific guidelines ranged between 58 and 100%. These consensus guidelines will improve equity of access to appropriate RDH and assist the planning of future storage requirements in New South Wales. [source] Autologous stem cell transplantation as treatment modality in a patient with relapsed pancreatoblastoma,PEDIATRIC BLOOD & CANCER, Issue 3 2010Amir Ali Hamidieh MD Abstract Pancreatoblastoma (PB) is a rare malignant neoplasm of the pancreas, which occurs mostly during childhood. Presently, the optimal treatment strategy is neither clear nor uniform for patients in advanced stages, in particular those with metastasis, inoperable, or recurrent tumors. To our knowledge, until now, only one patient with PB has been treated with hematopoietic stem cell transplantation (HSCT) following aggressive chemotherapy and surgical resection. Here we report the second case of PB who was treated with aggressive chemotherapy combined with autologous peripheral blood stem cell transplantation. Pediatr Blood Cancer. 2010;55:573,576. © 2010 Wiley-Liss, Inc. [source] Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 yearsBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2001Ashraf Badros The feasibility and efficacy of autologous stem cell transplantation (auto-SCT) in patients aged ,,70 years was analysed. Newly diagnosed (n = 34) and refractory multiple myeloma (n = 36) patients were studied. The median age was 72 years (range: 70,82·6). CD34+ cells were mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF) (n = 35) or G-CSF alone (n = 35), yielding medians of 11·8 × 106 versus 8 × 106cells/kg respectively (P = 0·007). Because of excessive mortality (16%) in the first 25 patients who received melphalan 200 mg/m2 (MEL-200), the dose was subsequently decreased to 140 mg/m2 (MEL-140). Median times to absolute neutrophil count (ANC) > 0·5 × 109/l and to platelets >,20 × 109/l were 11 and 13 d respectively. Thirty-one patients (44%) received tandem auto-SCT. Complete remission (CR) was 20% after the first SCT and 27% after tandem SCT. Median CR duration was 1·5 years and was significantly longer for patients with ,,12 months of prior chemotherapy (2·6 versus 1·0 years, P = 0·0008). The 3-year event-free survival (EFS) and overall survival (OS) (+ standard error, SE) were projected at 20% + 9% and 31% + 10% respectively. Tandem SCTs positively affected EFS (4·0 versus 0·7 years; P = 0·003) and OS (4·0 versus 1·4 years; P = 0·02) compared with single auto-SCT. In conclusion, MEL-140 is less toxic and appears equally as efficacious as MEL-200 in elderly patients. The benefits of tandem SCT in this patient population need further evaluation in a randomized trial. [source] First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitroEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2010Thomas Lund Abstract Objectives:, The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma. Methods:, Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results:, Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions:, Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. [source] Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Fortunato Morabito Abstract The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression-free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are assessing whether MP plus lenalidomide or the combination of lenalidomide plus dexamethasone should be considered an attractive treatment option, while additional studies are needed to determine the role of routine maintenance or consolidation therapy with these new drugs. This new therapeutic armamentarium in light of adequate prophylaxis and supportive care allows clinicians to greatly improve the survival perspectives for both young and elderly patients. In this review, we report updated data for the front-line therapy of MM, examining the role of new drugs either when administered as induction therapy before ASCT in younger patients or when combined with alkylating agents for the treatment of older patients. The most relevant articles on therapy of MM published from November 1982 to January 2010 (selected through PubMed), and recent meeting abstracts were used as sources for this review. [source] ThaDD plus high dose therapy and autologous stem cell transplantation does not appear superior to ThaDD plus maintenance in elderly patients with de novo multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2010Massimo Offidani Abstract Objectives:,With the aim to address the issue whether high-dose therapy (HDT) is required after new drugs combinations to improve outcome of elderly newly diagnosed multiple myeloma (MM) patients, we compared the toxicity and the outcome of ThaDD plus maintenance to those of ThaDD plus HDT-autologous stem cell transplantation (ASCT). Methods: Sixty-two patients not eligible for HDT receiving six courses of ThaDD regimen plus maintenance with thalidomide were compared to 26 patients eligible for HDT treated with four courses of ThaDD followed by melphalan 100,200 mg/m2 and ASCT. The two groups were matched for the main characteristics except for age favouring the HDT group. Results and conclusions:,Complete remission (CR) obtained with ThaDD plus maintenance was 24% whereas it was 57% after ThaDD plus HDT-ASCT (P = 0.0232). However, after a median follow-up of 36 months, median time to progression (TTP) and progression free survival (PFS) of the group of patients undergone HDT were not significantly different to those of patients receiving ThaDD plus maintenance (32 vs. 31 months: P = 0.962; 32 vs. 29 months: P = 0.726, respectively). Five-year overall survival (OS) was 49% in the first group and 46% in the latter one (P = 0.404). As expected, a significantly higher incidence of grade 3,4 neutropenia, thrombocytopenia, infections, mucositis and alopecia were observed in the ThaDD plus HDT group. Our results suggest that in elderly MM patients ThaDD plus HDT, albeit significantly increases CR rate, seems to be equivalent to ThaDD plus maintenance in terms of TTP, PFS and OS. These results challenge the requirement for HDT consolidation in this subset of patients. [source] High risk of hepatitis B-virus reactivation after hematopoietic cell transplantation in hepatitis B core antibody-positive patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2009Kosei Matsue Abstract We investigated the serological changes in hepatitis B virus (HBV)-related markers in 55 and 26 hepatitis B surface antigen (HBsAg)-negative patients undergoing allogeneic and autologous stem cell transplantation, respectively, over the past 4 yr. Five of the 17 allogeneic and one of the five autologous patients with pretransplant anti-hepatitis B core antigen antibodies (anti-HBc) were HBsAg-positive after transplantation, whereas none of the patients negative for anti-HBc were HBsAg-positive in both groups. All patients who became HBsAg-positive received steroid-containing immunosuppressive therapy for chronic graft versus host disease (GVHD) or myeloma. Four of the six patients developed flare of HBV hepatitis, and two patients did not. One patient developed fulminant hepatitis treated with lamivudine and plasma exchange. Other five patients received entecavir from the detection of HBsAg. Although HBV-DNA levels became below the limit of detection in all patients, HBsAg positivity remained in three patients after 6 months of treatment. We concluded that anti-HBc positivity is a risk factor for reactivation of HBV after both autologous and allogeneic transplantation, and HBV-related markers should be monitored regularly in these patients. We also stress the efficacy of pre-emptive use of antiviral agents in controlling HBV replication and limiting hepatic injury due to reactivation of HBV in these patients. [source] Serum vascular endothelial growth factor in adult haematological patients with neutropenic fever: a comparison with C-reactive proteinEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2009Sari Hämäläinen Abstract Objectives:, Vascular endothelial growth factor (VEGF) is considered to be of importance in patients with sepsis. No data are available on VEGF kinetics in haematological patients with neutropenic fever. Methods:, Forty-two haematological patients were included into this prospective study. Median age was 57 yr (range 18,70). Fifteen patients received therapy for acute myeloid leukaemia and 27 patients received autologous stem cell transplantation for haematological malignancy. Laboratory samples for the determination of C-reactive protein (CRP) and VEGF were collected at the start of fever (d0) and then daily. Results:, The median serum VEGF concentrations were low in all study patients. In patients with severe sepsis (n = 5) the median VEGF on d0 was higher than in septic patients without signs of hypoperfusion or hypotension (n = 37) (77 pg/mL vs. 52 pg/mL, P = 0.061). Also on d1 the median VEGF concentration was higher in patients with severe sepsis (82 pg/mL vs. 56 pg/mL, P = 0.048). There were no statistically significant differences in CRP values on any day during the study period between patients with severe sepsis and those without. Time from d0 to the peak VEGF concentration (mean 1.02, SE 0.18 d) was shorter than that to the peak CRP concentration (mean 1.93, SE 0.15 d) (P = 0.002). Conclusion:, Compared to CRP, serum VEGF was a more rapid indicator for sepsis in our haematological patients with neutropenic fever. Those with severe sepsis had higher VEGF concentrations than those without on d0 and d1 after the onset of fever. Further studies on VEGF are warranted in haematological patients. [source] High-dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B-cell lymphomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008Mehdi Hamadani Abstract The transformation of follicular lymphoma (FL) to high-grade histology occurs in up to 70% of patients. The role of hematopoietic stem cell transplantation (HSCT) in transformed FL is poorly defined. Twenty-four FL patients with histologically confirmed transformation to diffuse large B-cell lymphoma underwent unpurged autologous HSCT at our institution. Their median age was 56 yr. The median number of prior chemotherapies was 2 (range 1,6). Thirteen patients had residual nodal disease measuring more than 2 cm and four patients had bulky disease at the time of HSCT. Six patients had refractory disease at transplantation. At a median follow-up of 38 months, 3-yr progression-free survival following autologous HSCT was 40%. The 3-yr overall survival was 52%. The cumulative incidence of relapse and non-relapse mortality rate was 41% and 25%, respectively. [source] Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high-dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomasEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007P. Schütt Abstract High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of ,2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab. [source] Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosageEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006A. Clopés Abstract:,Background:,Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. Patients and methods:,Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. Results:,Mean BU exposure (AUCss) (±DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade , II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. Conclusions:,The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD. [source] Successful unrelated cord blood transplantation in a 7-year-old boy with Evans syndrome refractory to immunosuppression and double autologous stem cell transplantationEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Christian Urban Abstract:, Evans syndrome is an autoimmunopathy characterized by thrombocytopenia and autoimmune hemolytic anemia with poor response to immunosuppression. A 2-yr-old boy with Evans syndrome showed only short-lasting responses to immunosuppressive treatment including double autologous peripheral stem cell transplantation (SCT). Intracranial bleeding required emergency splenectomy and external ventricular drainage. Unrelated umbilical cord blood was given following conditioning with busulfan, thiotepa, etoposide and antithymocyte globulin. One year after SCT the patient shows stable blood counts without immunosuppression. This is the first child reported with Evans syndrome successfully treated by means of unrelated cord blood transplantation. [source] Autologous transplantation in relapsed and refractory Hodgkin's diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2005Andreas Josting Abstract:, The current data support the use of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard procedure for the majority of patients with Hodgkin's disease (HD) relapsing or progressing after combination chemotherapy. Prognostic factors reflecting unfavourable prognostic features of the disease as well as resistance to conventional salvage therapy have been identified. Preliminary data suggests a high efficacy of high-dose sequential chemotherapies in these patients. An ongoing randomized trial is comparing standard HDCT versus sequential HDCT in patients with relapsed HD. [source] PET-CT imaging of combined brachial and lumbosacral neurolymphomatosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2005Pazit Kanter Abstract:, Neurolymphomatosis is a rare manifestation of progressive non-Hodgkin's lymphoma. A 44-yr-old man with diffuse large B-cell lymphoma presented with unilateral progressive peripheral sensorimotor neuropathy after the 7th cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. No pathology in the nervous system was evident by computerized tomography (CT), magnetic resonance imaging (MRI) of the head, spinal axis and plexuses and by repeated analysis of cerebrospinal fluid. However, the hybrid modality of positron emission tomography (PET) of fluorinated deoxyglucose (FDG) combined with CT scan (PET-CT) showed unilateral involvement of both the brachial and lumbosacral nervous plexuses. A complete recovery of neurological manifestations and normalization of PET-CT followed intensive chemotherapy with autologous stem cell transplantation. The diagnosis and localization of neurolymphomatosis may be supported by PET-CT imaging. [source] Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalanEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2004Yasukazu Kawai Abstract: Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity. [source] Intravascular lymphoma: a neoplasm of ,homeless' lymphocytes?HEMATOLOGICAL ONCOLOGY, Issue 3 2006Maurilio Ponzoni Abstract Intravascular lymphoma (IVL) is an extremely rare form of non-Hodgkin lymphoma characterized by almost exclusive growth of neoplastic lymphocytes within blood vessel lumen. IVL is morphologically characterized in most instances by large cells with B-cell lineage. IVL is an aggressive and usually disseminated disease that predominantly affects elderly patients, resulting in poor PS, B-symptoms, anemia, and high lactate dehydrogenase serum level. The brain and skin are the most commonly involved sites; nodal disease is rare. Survival after conventional chemotherapy is disappointing, with a relevant impact of diagnostic delay and lethal complications. Notwithstanding these results, IVL limited to the skin (cutaneous variant) is a favorable presentation with distinctive clinical characteristics. Moreover, differences in clinical presentation with Eastern Countries IVL cases, mostly associated with hemophagocytic syndrome, do exist. Intensive combinations containing drugs with higher central nervous system bioavailability are needed in cases with brain involvement; the role of high-dose chemotherapy with autologous stem cell transplantation should be investigated in younger patients with unfavorable features. The present review will discuss the most recent acquisitions related either to diagnosis and immunophenotypic/biologic characteristics as well as clinical/therapeutic issues of IVL. Copyright © 2006 John Wiley & Sons, Ltd. [source] Peripheral blood stem cell collection in multiple myeloma: A retrospective analysis of 6 years leukapheresis activity in 109 patients treated at the Istituto Nazionale dei Tumori of MilanJOURNAL OF CLINICAL APHERESIS, Issue 4 2009Paola Coluccia Abstract Double autologous stem cell transplantation is the standard treatment in newly diagnosed multiple myeloma (MM) patients younger than 65 years; therefore, optimization of leukapheresis is crucial. We performed a retrospective analysis of 297 leukaphereses comparing semiautomated (V4.7 in 20% of collections) versus automated (V6.0 in 80%) Caridian (COBE) Spectra versions and analyzing the influence of M-protein on the outcome. Both methods gave comparable collection efficiencies (CE%) (53.4% vs. 55.7% in V6.0 and V4.7, respectively) with similar leukapheresis time and processed volume. Harvest volume was higher in V4.7 (P < 0.0001) with similar contamination of red blood cells (RBCs) (P = 0.77) and platelets (P = 0.09) when compared with V6.0. In patients with higher peripheral white blood cells (WBCs), V6.0 with adjusted harvest volume (<700 mL), achieved similar CD34+ CE% (P = 0.39) and better enrichment of nucleated cells (P < 0.0,002) but higher RBCs (P < 0.0,001) and platelets contamination (P = 0.001), when compared with a larger cycle volume in patients with lower WBCs. In hard to mobilize patients, CD34+ CE% was significantly more efficient with V4.7 than V6.0 (P < 0.0,001). CD34+ CE% was unaffected by serologic M-protein, but platelet CE% was higher in the absence of M-protein (P = 0.0,003), without any reduction in peripheral patients platelets. We, therefore, conclude that in the setting of MM patients with a high WBCs count and/or low percentage of peripheral CD34+ cells, collections with V4.7 or adjusted cycle volume V6.0 gave comparable result in CD34+ CE%. RBCs and platelets contamination is higher if low cycle volume is chosen. In hard to mobilize patients, V4.7 is advisable. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] The number of CD34+ cells in peripheral blood as a predictor of the CD34+ yield in patients going to autologous stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 2 2006A.L. Basquiera Abstract The number of CD34+ cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34+ cells in PB that allows achieving a final apheresis product containing ,1.5 × 106 CD34+ cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1,3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34+ cells count in peripheral blood and the CD34+ cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34+ cells in PB to obtain ,1.5 × 106/kg in the first apheresis was 16.48 cells/,L (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/,L, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, ,15 CD34+ cells/,L is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 × 106/kg CD34+ cells in the graft with ,3 collections. J. Clin. Apheresis 2005. © 2005 Wiley-Liss, Inc. [source] Idiotype-pulsed antigen presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Martha Q. Lacy Vaccines are attractive as consolidation therapy after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We report the results of a phase II trial of the immunotherapeutic, APC8020 (MylovengeÔ), given after ASCT for MM. We compared the results with that of other patients with MM who underwent ASCT at Mayo Clinic during the same time period. Twenty-seven patients were enrolled on the trial between July, 1998 and June, 2001, and the outcomes were compared to that of 124 consecutive patients transplanted during the same period, but not enrolled on the trial. The median (range) follow-up for patients still alive from the vaccine trial is 6.5 (2.9,8 years), and 7.1 (6,8 years) in the control group. The median age was 57.4 range (36.1,71.3) in the DB group and 56.4 (range, 30,69) in the trial group. Known prognostic factors including PCLI, B2M, and CRP were comparable between the groups. The median overall survival for the trial patients was 5.3 years (95% CI: 4.0 years,N/A) compared to 3.4 years (95% CI: 2.7,4.6 years) for the DB group (P = 0.02). The median time to progression and progression-free survival for the trial group was similar to the DB group. Although not a controlled trial, the vaccines given after ASCT appear to be associated with improved overall survival compared to historical controls. This approach warrants further investigation to confirm this and define the role of vaccine therapy in myeloma. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Hideki Nakasone The combination of cyclophosphamide and granulocyte-colony stimulating factor (G-CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently, however, alternative approaches such as G-CSF alone or etoposide followed by G-CSF have been investigated. We, therefore, retrospectively analyzed the effects of these mobilization methods on collection yield and disease outcome in ASCT for MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For mobilization, 67, 58, and 21 patients received cyclophosphamide and G-CSF, etoposide and G-CSF, and G-CSF alone (including nonmyelosuppressive chemotherapy followed by G-CSF), respectively. Among them, 136 achieved the target number of HSCs (at least 2 × 106/kg). Lower creatinine and higher albumin levels at diagnosis were significantly associated with successful yield. A lower number of infused HSCs, use of the etoposide for mobilization and high ISS were associated with delayed hematopoietic recovery. The mobilization methods did not significantly affect either the successful collection of more than 2 × 106 CD34-positive cells/kg or PFS after ASCT. G-CSF alone was sufficient for stem cell mobilization for a single ASCT. The optimal approach to collect HSCs in MM remains to be elucidated. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] High-dose therapy and autologous stem cell transplantation for children with HIV-associated non-Hodgkin lymphomaPEDIATRIC BLOOD & CANCER, Issue 7 2007Simon Fluri MD Abstract In contrast to adults, autologous stem cell transplantation (ASCT) as part of the salvage strategy after high-dose chemo/radiotherapy in human immunodeficiency virus (HIV) related Non-Hodgkin lymphoma (NHL) is not yet established for children. We report on a 13-year patient with congenital HIV infection and refractory Burkitt lymphoma, who was successfully treated by high-dose therapy (HDT) including rituximab followed by ASCT. After 26 months follow-up the patient remains in complete remission and his HIV parameters have normalized with continued highly active antiretroviral therapy (HAART). HIV infection may no longer exclude children from ASCT as part of salvage therapy. Pediatr Blood Cancer 2007;49:984,987. © 2006 Wiley-Liss, Inc. [source] Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Paul M. Barr Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B-cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50 ,g/m2 given over 24 hr and vincristine 1.4 mg/m2 on days 1 and 15 every 28 days in aggressive B-cell non-Hodgkin lymphoma (NHL) relapsing after autologous stem cell transplantation. End points included tumor response, toxicity, and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with two patients achieving a complete response. The most common toxicities were Grade 3 lymphopenia (seven patients), Grade 3 to 4 neutropenia (two patients), and Grade 3 hypophosphatemia (two patients). Median progression-free and overall survivals for all patients were 5.7 and 21.4 months, respectively. One patient demonstrated an increase in T-cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine have efficacy in select patients with aggressive NHL. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T-cell apoptosis. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Poor hematopoietic stem cell mobilizers: A single institution study of incidence and risk factors in patients with recurrent or relapsed lymphomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2009Chitra Hosing The purpose of this retrospective study was to determine the incidence and predictive factors if any, of mobilization failure in lymphoma patients referred for autologous stem cell transplantation. A total of 588 lymphoma patients were referred for transplant consultation from January 2003 to December 2004. Predictors of mobilization failure were evaluated using logistic regression analysis including diagnosis, mobilization regimen, age, sex, type and number of prior chemotherapies, bone marrow cellularity, platelet count, white count, prior bone marrow involvement with malignancy, and prior radiation therapy. Two hundred and six patients were eligible for transplantation and underwent stem cell mobilization. Twenty-nine (14%) patients failed to mobilize adequate stem cells after the first attempt. For the entire group age (,60 versus <60 years), diagnosis (Hodgkin's versus non-Hodgkin's lymphoma), use of cytokines alone, platelet count <150 × 109/L, and bone marrow cellularity <30% were significant predictors for mobilization failure on univariate analysis. In view of small number of patients multivariate analysis was not possible. However, a low platelet count (150 × 109/L) was the only significant predictor when the analysis was restricted to non-Hodgkin's lymphoma patients who were mobilized with chemotherapy. Mobilization failure rates are higher in patients with non-Hodgkin's lymphoma compared with those with Hodgkin's lymphoma. In the subset of patients who undergo chemomobilization for non-Hodgkin's lymphoma platelet count at the time of mobilization is a predictor of mobilization failure. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Combinations of cytogenetics and international scoring system can predict poor prognosis in multiple myeloma after high-dose chemotherapy and autologous stem cell transplantation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Yoshihiro Inamoto High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy for newly diagnosed multiple myeloma. Combinations of recently proposed prognostic factors such as cytogenetics and international scoring system (ISS) may be useful to predict prognosis after ASCT. This study evaluated 60 consecutive patients who underwent ASCT in four institutes. The median age of patients was 57 years old. Cytogenetic analyses of bone marrow at diagnosis detected metaphase abnormalities in 9 of 51 patients and interphase abnormalities in six of 35 patients (17p13 deletion, t(4;14) and t(14;16)). Seventeen patients had ISS stage 3 at diagnosis. Twenty-five patients who had any of these risk factors were defined as high risk. All patients were conditioned with high-dose melphalan. With a median follow-up of 3.4 years, overall survival and event-free survival at 3 years were significantly worse in high-risk patients (48% vs. 97%; P = 0.0005 and 16% vs. 37%; P = 0.038, respectively) despite the higher CR plus VGPR rate among high-risk patients. In addition, survival at 1 year after progression was significantly worse in high-risk patients despite salvage chemotherapy containing thalidomide (32% vs. 100%, P = 0.0001). Combinations of cytogenetics and ISS could readily predict prognosis. Quality of response is a poor surrogate marker for ultimate outcome. High-risk patients may need more effective treatment. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large B-cell lymphomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2009Luis F. Porrata Peripheral blood absolute lymphocyte count (ALC) is a survival prognostic factor in hematological malignancies. No reports have addressed whether ALC at the time of first relapse (ALC-R) predicts survival. Thus, we assessed the prognostic significance of ALC-R in diffuse large B-cell lymphoma (DLBCL). Patients were required to have been diagnosed with first relapsed DLBCL, have ALC-R values, and to be followed at Mayo Clinic, Rochester. From Feb 1987 until March 2006, 97 first relapsed DLBCL patients qualified for the study. The overall survival (OS) and progression-free survival (PFS) were measured from the time of first relapse. The value of ALC- R , 1.0 × 109/L was used for the analysis. Both groups (ALC-R , 1 or < 1 × 109/L) were balanced for the international prognostic index at relapse (IPI-R) (P = 0.3), and for autologous stem cell transplantation (P = 0.4). Superior OS and PFS were observed with an ALC-R , 1.0 × 109/L (N = 60) versus ALC-R < 1.0 × 109/L (N = 37) [median OS: 28.7 months, 5 years OS rates of 39% versus median OS: 10.2 months, 5 years OS rates of 14%, P < 0.002; and median PFS: 14.8 months, 5 years PFS rates of 21% versus median PFS: 6.5 months, 5 years PFS rates of 8%, P < 0.004, respectively]. ALC-R was an independent prognostic factor for OS [RR = 0.4, P < 0.01] and PFS [RR = 0.5, P < 0.005]. ALC-R predicts survival suggesting that host immunity is an important variable predicting survival in first relapsed DLBCL. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] Conventional allogeneic hematopoietic stem cell transplantation for lymphoma may overcome the poor prognosis associated with a positive FDG-PET scan before transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2008Akihide Yoshimi A positive scan in pretransplantation fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be associated with a poor prognosis in patients with lymphoma undergoing high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). For those with a positive FDG-PET scan, treatment that includes allogeneic stem cell transplantation (allo-SCT) may be an alternative. However, it is uncertain whether allo-SCT can overcome a poor prognosis. Therefore, we conducted a retrospective analysis of 14 patients with lymphoma who had undergone FDG-PET scan within one month before allo-SCT at our institution. Eleven patients were FDG-PET-positive and three were negative. With a median follow-up of 17 months (range: 6,44) after allo-SCT, the cumulative incidence of progression was 29.3% in FDG-PET-positive patients and 0% in the FDG-PET-negative patients. Four of the 11 patients who had post-transplantation FDG-PET showed FDG-avid lesions on the first post-transplantation scan. In two of the four, regression of the lesions was observed during the scheduled reduction of immunosuppressant without donor lymphocyte infusion and remained without progression at the last follow-up (34 and 8 months). Durable responses after allo-SCT, at least with conventional conditioning regimens, can be expected in patients with FDG-PET-positive lesions before transplantation. Thus, conventional allo-SCT could be an attractive modality compared to ASCT for patients with positive FDG-PET after the completion of conventional salvage chemotherapy, and particularly for patients with T and NK-cell lymphomas. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Successful treatment of pure red cell aplasia with autologous stem cell transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2007Jae H. Park We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was intolerant of conventional immunosuppressive therapies but achieved a complete long-term remission following autologous hematologic stem cell transplant (HSCT). The patient was initially treated with high-dose prednisone, cyclophosphamide, cyclosporine, antithymocyte globulin, and then rituximab. With the exception of rituximab, all of the above regimens achieved a transient response. However, because of the persistent requirement for red blood cell transfusions and intolerance to the multiple immunosuppressive therapies, autologous HSCT was eventually performed. The patient remains in complete remission and on no other therapy for 36 months following the autologous HSCT. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Successful Long-Term Outcome of the First Combined Heart and Kidney Transplant in a Patient with Systemic AL AmyloidosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009V. Audard Simultaneous cardiac and renal involvement is associated with a particularly poor prognosis in patients with AL amyloidosis (AL-A). We report the first case of a successful long-term outcome of combined heart and kidney transplantation not followed by autologous stem cell transplantation in a patient with systemic AL-A. The recipient was a 46-year-old man with end-stage renal failure associated with serious cardiac involvement in the context of AL-A. Before transplantation, two courses of oral melphalan plus prednisone induced partial hematologic remission, as shown by the decrease in circulating free light chain with no improvement of renal or heart function. The patient underwent combined heart and kidney transplantation as a rescue treatment. During the follow-up period (36 months), plasma cell dyscrasia remains in complete remission, with normal free lambda light chain levels and no recurrence of amyloid deposition on heart and kidney grafts. This case report demonstrates that combined heart and kidney transplantation not systematically associated with stem cell transplantation may be considered an additional therapeutic option in AL-A patients with severe organ dysfunction and partial hematologic remission. [source] Magnetization transfer ratio evolution with demyelination and remyelination in multiple sclerosis lesionsANNALS OF NEUROLOGY, Issue 2 2008Jacqueline T. Chen PhD Objective To assess demyelination and remyelination in vivo in acute gadolinium (Gd)-enhancing lesions of multiple sclerosis (MS). Methods We measured significant changes in magnetization transfer ratio (MTR) consistent with demyelination and remyelination of individual lesion voxels, as well as the mean normalized MTR over all lesion voxels during and after contrast enhancement, in MS patients participating in a 3-year Canadian trial assessing immunoablation and autologous stem cell transplantation for treatment of MS. Results The average mean normalized lesion MTR over all lesions exhibited partial recovery over 2 to 4 months after Gd enhancement. Voxel-based analysis demonstrated that approximately 70% of the initially enhancing lesion volume (GdLV) was left with stably low MTR over 39 months of evaluation. The percentage of the GdLV undergoing significant increases in MTR consistent with remyelination increased for approximately 7 months after enhancement and then stabilized at 21 %GdLV. Significant decreases in MTR consistent with demyelination were ongoing for approximately 33 months after enhancement, stabilizing at 9 %GdLV. The estimated error of these measurements, based on scan/rescan analysis, was less than 0.4 %GdLV. Interpretation We found significant changes in MTR consistent with demyelination and remyelination that followed different temporal evolutions and were ongoing in different lesion regions for at least 3 years after lesion formation. Ann Neurol 2008 [source] Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma: a retrospective studyBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Hilmi Ege Summary Absolute lymphocyte count (ALC) recovery after autologous stem cell transplantation for multiple myeloma (MM) has been reported to be an independent prognostic factor for clinical outcome. The role of ALC on survival in newly diagnosed untreated MM patients is unknown. Between 1994 and 2002, we analysed retrospectively 537 MM patients of 1835 consecutive MM patients that were neither uniformly treated nor part of a clinical trail, but originally diagnosed and followed at the Mayo Clinic. The primary endpoint was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). The median follow-up was 35·1 months (range: 1,152·5 months). ALC, as a continuous variable, was identified as prognostic factor for OS (Hazard ratio = 0·473, 95% confidence interval = 0·359,0·618, P < 0·0001). MM patients with an ALC ,1·4 × 109/l experienced superior OS compared with MM patients with an ALC <1·4 × 109/l (65 vs. 26 months, P < 0·0001). Multivariate analysis identified ALC as an independent prognostic factor for OS. This study showed that, in newly diagnosed MM, ALC is an independent prognostic factor for OS, suggesting a significant role of host immune status in the survival of MM. [source] | |||||||||||||||||||||||||