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1.
Bone Marrow Transplant ; 50(12): 1519-25, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26367229

ABSTRACT

Umbilical cord blood (UCB) as an allogeneic transplant source is generally limited to units with pre-cryopreservation total nucleated cell (TNC) doses ⩾2.5 × 10(7) NC/kg. We prospectively investigated single UCB transplantation, with cord units as low as 1 × 10(7) NC/kg, all processed with post-thaw albumin-dextran dilution. We transplanted 104 adult patients with 84% having relapsed/refractory disease. The median TNC dose was 2.1 × 10(7) NC/kg (range: 1.0-4.4 × 10(7)) and median CD34+ cell dose was 1.0 × 10(5)/kg (range: 0.0-3.7 × 10(5)/kg). Post-manipulation cell recovery and viability were 96% and 99%, respectively. Median times to neutrophil and platelet engraftment were 16 and 43 days, respectively. Univariate factors predicting neutrophil engraftment included TNC (P=0.03) and CD34+ cell dose (P=0.01). CD34+ dose predicted platelet engraftment (P<0.001). In multivariate analysis, CD34+ dose remained significant for neutrophil and platelet engraftment (P<0.0001 and P<0.0001, respectively). The 100-day and 1-year overall survival were 70% and 46%, respectively (95% confidence interval: 36%-56% at 1 year). The subset transplanted with 1-1.5 × 10(7) NC/kg had similar 100-day and 1-year survivals of 73% and 45%, respectively. Single-unit UCB transplantation using small units, processed as described, leads to favorable engraftment and acceptable outcomes in poor prognosis patients. CD34+ cell dose (⩾1.5 × 10(5)/kg) helps predict faster engraftment and can aid in graft selection.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematologic Neoplasms/blood , Hematologic Neoplasms/therapy , Recovery of Function , Adolescent , Adult , Aged , Allografts , Female , Humans , Leukocyte Count , Male , Middle Aged , Platelet Count , Prospective Studies
2.
Ann Oncol ; 25(3): 669-674, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24567515

ABSTRACT

BACKGROUND: The role of body mass index (BMI) in survival outcomes is controversial among lymphoma patients. We evaluated the association between BMI at study entry and failure-free survival (FFS) and overall survival (OS) in three phase III clinical trials, among patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin's lymphoma (HL). PATIENTS AND METHODS: A total of 537, 730 and 282 patients with DLBCL, HL and FL were included in the analysis. Baseline patient and clinical characteristics, treatment received and clinical outcomes were compared across BMI categories. RESULTS: Among patients with DLBCL, HL and FL, the median age was 70, 33 and 56; 29%, 29% and 37% were obese and 38%, 27% and 37% were overweight, respectively. Age was significantly different among BMI groups in all three studies. Higher BMI groups tended to have more favorable prognosis factors at study entry among DLBCL and HL patients. BMI was not associated with clinical outcome with P-values of 0.89, 0.30 and 0.40 for FFS, and 0.64, 0.67 and 0.09 for OS, for patients with DLBCL, HL and FL, respectively. The association remains non-significant after adjusting for other clinical factors in the Cox model. A subset analysis of males with DLBCL treated on R-CHOP revealed no differences in FFS (P = 0.48) or OS (P = 0.58). CONCLUSION: BMI was not significantly associated with clinical outcomes among patients with DLBCL, HD or FL, in three prospective phase III clinical trials. The findings contradict some previous reports of similar investigations. Further work is required to understand the observed discrepancies.


Subject(s)
Body Mass Index , Hodgkin Disease/mortality , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Obesity/mortality , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Female , Hodgkin Disease/drug therapy , Humans , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Prednisone/therapeutic use , Prospective Studies , Rituximab , Treatment Outcome , United States , Vincristine/therapeutic use
3.
Bone Marrow Transplant ; 48(8): 1056-64, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23419433

ABSTRACT

Although the role of autologous hematopoietic cell transplantation (auto-HCT) is well established in neuroblastoma (NBL), the role of allogeneic HCT (allo-HCT) is controversial. The Center for International Blood and Marrow Transplant Research conducted a retrospective review of 143 allo-HCT for NBL reported in 1990-2007. Patients were categorized into two different groups: those who had not (Group 1) and had (Group 2) undergone a prior auto-HCT (n=46 and 97, respectively). One-year and five-year OS were 59% and 29% for Group 1 and 50% and 7% for Group 2, respectively. Among donor types, disease-free survival (DFS) and OS were significantly lower for unrelated transplants at 1 and 3 years but not at 5 years post HCT. Patients in CR or very good partial response (VGPR) at transplant had lower relapse rates and better DFS and OS, compared with those not in CR or VGPR. Our analysis indicates that allo-HCT can cure some neuroblastoma patients, with lower relapse rates and improved survival in patients without a history of prior auto-HCT as compared with those patients who had previously undergone auto-HCT. Although the data do not address why either strategy was chosen for patients, allo-HCT after a prior auto-HCT appears to offer minimal benefit. Disease recurrence remains the most common cause of treatment failure.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Neuroblastoma/surgery , Adolescent , Adult , Child , Child, Preschool , Data Collection , Disease-Free Survival , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Middle Aged , Retrospective Studies , Survival Rate , Transplantation, Autologous , Transplantation, Homologous , Treatment Outcome , Young Adult
4.
Bone Marrow Transplant ; 48(1): 85-93, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22732699

ABSTRACT

We evaluated immune reconstitution in 58 adults who received hematopoietic SCTs from allogeneic siblings (allosib), matched unrelated donors (MUD) or cord blood (CB) at 90-day intervals for 1 year post transplant. CB recipients had a higher incidence of infections in the first 100 days compared with allosib and MUD recipients. The number of circulating T cells was lower in CB recipients compared with MUD recipients at 90 days and compared with allosib recipients at 180 days. Spectratype analysis of the TCR Vß complementarity determining region 3 (CDR3) of patient lymphocytes revealed that the TCR repertoire remained poorly diversified even at 360 days in nearly all patients. In contrast, the number of circulating B cells was significantly elevated in CB recipients compared with allosib recipients throughout the first year post transplant and compared with MUD recipients at 9-12 months. Spectratype analysis of the B-cell receptor V(H) CDR3 showed that the B-cell repertoire was diversified in most patients by 90 days. CD5(pos) B cells from assayed CB recipients expressed intracellular IL-10 early post transplant. Our data suggest that B cells, in addition to T cells, may have a role in impaired immune responses in CB transplant patients.


Subject(s)
B-Lymphocytes/immunology , Cord Blood Stem Cell Transplantation/adverse effects , Graft vs Host Disease/immunology , Immunocompromised Host , Opportunistic Infections/immunology , Adult , Aged , B-Lymphocytes/metabolism , CD5 Antigens/blood , CD5 Antigens/genetics , CD5 Antigens/metabolism , Complementarity Determining Regions/blood , Complementarity Determining Regions/chemistry , Complementarity Determining Regions/genetics , Complementarity Determining Regions/metabolism , Female , Graft vs Host Disease/blood , Graft vs Host Disease/epidemiology , Graft vs Host Disease/metabolism , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Illinois/epidemiology , Incidence , Interleukin-10/metabolism , Male , Middle Aged , Opportunistic Infections/blood , Opportunistic Infections/epidemiology , Opportunistic Infections/metabolism , Receptors, Antigen, B-Cell/blood , Receptors, Antigen, B-Cell/chemistry , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/metabolism , Receptors, Antigen, T-Cell/blood , Receptors, Antigen, T-Cell/chemistry , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Siblings , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Transplantation, Homologous
5.
Bone Marrow Transplant ; 48(6): 777-81, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23178544

ABSTRACT

Before US regulatory approval, an expanded access program provided plerixafor to patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma (MM) who had not previously failed mobilization and were otherwise candidates for auto-SCT. Patients received granulocyte-CSF (G-CSF) 10 mcg/kg daily and plerixafor 0.24 mg/kg starting on day 4 with apheresis on day 5; all repeated daily until collection was complete. Overall, 104 patients received 1 dose of plerixafor. The addition of plerixafor to G-CSF resulted in a median threefold increase in peripheral blood CD34+ cell count between days 4 and 5. Among 43 NHL patients, 74% met the target of 5 × 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-5 days); among 7 HD patients, 57% met the target of 5 × 10(6) CD34+ cells/kg (median, 2 days apheresis, range 1-3); and among 54 MM patients, 89% met the target of 6 × 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-4). Overall, 93% of patients had 2 × 10(6) CD34+ cells/kg collected within 1-3 days. Plerixafor-related toxicities were minimal. Engraftment kinetics, graft durability and transplant outcomes demonstrated no unexpected outcomes. Efficacy and safety results were similar to results in phase II and III clinical trials.


Subject(s)
Anti-HIV Agents/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells , Heterocyclic Compounds/administration & dosage , Hodgkin Disease/therapy , Lymphoma, Non-Hodgkin/therapy , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation , Adult , Aged , Anti-HIV Agents/adverse effects , Benzylamines , Blood Component Removal , Cyclams , Female , Granulocyte Colony-Stimulating Factor/adverse effects , Heterocyclic Compounds/adverse effects , Hodgkin Disease/blood , Humans , Lymphoma, Non-Hodgkin/blood , Male , Middle Aged , Multiple Myeloma/blood , Retrospective Studies , Time Factors , Transplantation, Autologous , United States
6.
Bone Marrow Transplant ; 47(12): 1577-82, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22562082

ABSTRACT

The Functional Assessment of Cancer Therapy-Bone Marrow Transplant measures quality of life (QOL) in SCT patients. Prior reports found mixed results regarding QOL differences among autologous and allogeneic SCT patients. In addition, there is a paucity of literature examining differences in QOL patterns over time between autologous and allogeneic patients. The present study examines differences in QOL between patients free of clinical depression undergoing autologous (n = 41) and allogeneic (n = 64) SCT during early stages of treatment. Despite clinical differences, autologous and allogeneic patients demonstrated similar changes in QOL. The exception was the Functional subscale which indicated worse QOL for allogeneic patients at discharge (F test = 4.61, df = 1, P < 0.05); allogeneic patients (Mean = 13.06, s.d. = 5.36) indicated they were less able to function at work and were less accepting of their illness than autologous patients (Mean = 16.02, s.d. = 6.73). There was a significant main effect for time on nearly all QOL subscales (P < 0.05) demonstrating decline during treatment and return to baseline by discharge; only the Social Well-Being scale did not significantly change over time. These results help to understand patients' response to SCT in the earliest stages and ultimately help identify patients at risk who could benefit from therapeutic interventions.


Subject(s)
Stem Cell Transplantation/psychology , Antidepressive Agents/administration & dosage , Depression/etiology , Double-Blind Method , Female , Humans , Male , Middle Aged , Neoplasms/psychology , Neoplasms/surgery , Quality of Life , Sertraline/administration & dosage , Transplantation, Autologous , Transplantation, Homologous , Treatment Outcome
7.
Bone Marrow Transplant ; 47(4): 556-61, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21691260

ABSTRACT

Non-compliance has received significant attention in medicine, yet few studies have examined its correlates in autologous hematopoietic SCT (AHSCT) patients. This study examined predictors of non-compliance in a sample of 151 AHSCT patients treated in an outpatient setting. Before AHSCT, participants completed a validated measure of mood and retrospective chart reviews were conducted to assess non-compliance during AHSCT, defined as refusal of oral hygiene, prescribed exercise programs, oral nutrition and/or prescribed medications. We found 121 patients (80%) were non-compliant with an aspect of the AHSCT regimen on 1 or more days; mean percentage of non-compliant days was 16.6 (s.d. 15.6). Men were more likely than women to be non-compliant (P<0.05); as were participants with an elevated depression score (P<0.05). Stepwise regression models identified significant predictors of non-compliance: gender, depression, global distress and nausea and vomiting severity (P-values all <0.01). Further analysis revealed that the interaction of the psychological variables with gender was a more robust predictor of non-compliance (P<0.001). For outpatient AHSCT, our findings suggest the need to broaden conceptualizations of risk factors for non-compliance and the importance of assessing patient barriers to compliance to ensure optimal treatment outcome.


Subject(s)
Ambulatory Care , Hematopoietic Stem Cell Transplantation , Neoplasms/therapy , Patient Compliance , Adult , Female , Humans , Logistic Models , Male , Middle Aged , Neoplasms/psychology , Sex Factors , Transplantation, Autologous , Treatment Refusal
8.
Bone Marrow Transplant ; 42(11): 723-31, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18711352

ABSTRACT

Murine studies using anti-T-cell antibodies for conditioning in allogeneic SCT demonstrate engraftment with low rates of GVHD. On the basis of this preclinical model, we conditioned 30 patients with advanced hematologic malignancies with rabbit antithymocyte globulin (ATG) and TBI, to reduce rates of fatal acute GVHD. Patients were enrolled in two sequential groups: cohort 1 received ATG 10 mg/kg in divided doses (days -4 to -1)+200 cGy TBI (n=16), and cohort 2 received ATG (days -10 to -7)+450 cGy TBI (n=14). Median donor blood chimerism for the combined group was 94, 93 and 93% in the first, second and third months after transplant. Only three developed grade II acute GVHD despite 43% of patients receiving unrelated donor transplants. One-year survival was 71+/-11 and 54+/-14%, respectively, in recipients of related and unrelated donor SCT. Donor lymphocyte infusions were needed in 12 patients for the management of relapse and for mixed donor-recipient chimerism in 4 patients. We conclude that 10 mg/kg ATG and TBI allows engraftment with a low risk of acute GVHD; however, further dose optimization of ATG is required to achieve a balance between GVHD and disease relapse.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Graft vs Host Disease/therapy , Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adult , Aged , Animals , Antilymphocyte Serum/metabolism , Cohort Studies , Female , Humans , Lymphocytes/cytology , Male , Middle Aged , Rabbits , Treatment Outcome
9.
Bone Marrow Transplant ; 41(10): 867-72, 2008 May.
Article in English | MEDLINE | ID: mdl-18246113

ABSTRACT

The aim of this study was to identify risk factors associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116 patients underwent ASCT in 1989-2000 and reported to the Center for International Blood and Marrow Transplant Research. Eighty patients (69%) received ASCT as first-line therapy and 36 (31%), for recurrent disease. Risk factors affecting ASCT were analyzed with use of the Cox regression method. Metastatic disease at diagnosis, recurrence prior to ASCT and performance score <90 were associated with higher rates of disease recurrence/progression. Five-year probabilities of PFS in patients with localized and metastatic disease at diagnosis who received ASCT as first-line therapy were 49% (95% CI 30-69) and 34% (95% CI 22-47) respectively. The 5-year probability of PFS in patients with localized disease at diagnosis, and received ASCT after recurrence was 14% (95% CI 3-30). PFS rates after ASCT are comparable to published rates in patients with similar disease characteristics treated with conventional chemotherapy, surgery and irradiation suggesting a limited role for ASCT in these patients. Therefore, ASCT if considered should be for high-risk patients in the setting of carefully controlled clinical trials.


Subject(s)
Myeloablative Agonists/therapeutic use , Sarcoma, Ewing/therapy , Stem Cell Transplantation/methods , Adolescent , Adult , Child , Combined Modality Therapy , Disease Progression , Female , Humans , Male , Middle Aged , Risk Factors , Sarcoma, Ewing/mortality , Sarcoma, Ewing/secondary , Survival Analysis , Transplantation, Autologous
10.
Bone Marrow Transplant ; 41(6): 537-45, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18084340

ABSTRACT

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.


Subject(s)
Breast Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Adult , Antineoplastic Agents/therapeutic use , Breast Neoplasms/mortality , Combined Modality Therapy , Disease-Free Survival , Female , Graft vs Host Disease/mortality , Graft vs Tumor Effect , Hematopoietic Stem Cell Transplantation/mortality , Humans , Middle Aged , Myeloablative Agonists/therapeutic use , Neoplasm Metastasis , Recurrence , Retrospective Studies , Survival Analysis , Transplantation, Homologous
11.
Ann Oncol ; 18(7): 1216-23, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17470451

ABSTRACT

BACKGROUND: Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin's lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety, pharmacokinetics, and efficacy were evaluated. PATIENTS AND METHODS: Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractory patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m(2)) and rituximab (375 mg/m(2)). International Workshop Response Criteria (IWRC) were used to evaluate response. RESULTS: Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics. CONCLUSION: These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Murine-Derived , Drug Resistance, Neoplasm , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Rituximab
12.
Transpl Infect Dis ; 9(2): 89-96, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17461992

ABSTRACT

We describe the clinical courses of 3 patients with hematologic malignancies (2 with acute myelogenous leukemia and 1 with multiple myeloma) who developed invasive fungal infections due to uncommon molds (Alternaria spp., Paecilomyces lilacinus, and Zygomycetes). Breakthrough invasive fungal infections of the sinus (n=1), lung (n=3), and pericardium (n=1) developed despite fluconazole prophylaxis and failed to respond to treatment with other licensed antifungal therapies, including amphotericin B (n=3), caspofungin (n=2), and voriconazole (n=3), and surgical intervention (n=2). Salvage therapy with posaconazole oral suspension resulted in successful outcomes in all 3 patients, who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) while on continued posaconazole therapy. The median duration of posaconazole treatment before HSCT was 5 months (range: 1.5-6 months). Posaconazole salvage therapy allowed successful allogeneic HSCT in 3 patients with refractory invasive mold infections.


Subject(s)
Antifungal Agents/therapeutic use , Mycoses/drug therapy , Triazoles/therapeutic use , Adult , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Multiple Myeloma/therapy , Prospective Studies , Salvage Therapy , Transplantation, Homologous
13.
Bone Marrow Transplant ; 39(1): 11-23, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17164824

ABSTRACT

Umbilical cord blood transplantation (UCBT) in adults is limited by the small number of primitive hematopoietic stem cells (HSC) in each graft, resulting in delayed engraftment post transplant, and both short- and long-term infectious complications. Initial efforts to expand UCB progenitors ex vivo have resulted in expansion of mature rather than immature HSC, confounded by the inability to accurately and reliably measure long-term reconstituting cells. Ex vivo expansion of UCB HSC has failed to improve engraftment because of resulting defects that promote apoptosis, disrupt marrow homing and initiate cell cycling. Here we discuss the future of ex vivo expansion, which we suggest will include the isolation of immature hematopoietic progenitors on the basis of function rather than surface phenotype and will employ both cytokines and stroma to maintain and expand the stem cell niche. We suggest that ex vivo expansion could be enhanced by manipulating newly discovered signaling pathways (Notch, Wnt, bone morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular mediators (phosphatase and tensin homolog and glycogen synthase kinase-3) in a manner that promotes HSC expansion with less differentiation. Improved methods for ex vivo expansion will make UCBT available to more patients, decrease engraftment times and allow more rapid immune reconstitution post transplant.


Subject(s)
Cell Differentiation/physiology , Cell Proliferation , Cord Blood Stem Cell Transplantation , Hematopoiesis/immunology , Hematopoietic Stem Cells/physiology , Adult , Apoptosis/immunology , Cell Culture Techniques , Cell Separation , Graft Survival/physiology , Hematopoietic Stem Cells/cytology , Humans , Recovery of Function/immunology , Signal Transduction/physiology , Time Factors , Transplantation, Homologous
14.
Bone Marrow Transplant ; 38(11): 757-64, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17057729

ABSTRACT

Outpatient hematopoietic stem cell transplants (HSCT) are usually performed in patients receiving minimally mucotoxic preparative regimens; total body irradiation (TBI)-based regimens typically are excluded. To improve resource utilization and patient satisfaction, we developed a totally outpatient HSCT program for TBI regimens and compared outcomes for our first 100 such transplants to 32 performed as in-patients during the same interval, for caregiver or financial reasons. Symptoms were managed predominately with oral agents; pain management consisted of transdermal fentanyl and oral morphine solution. Except for more unmarried in-patients, the two groups were matched. Time to engraftment, severity of mucositis and transplant duration were identical for the two groups. Twenty-seven of the outpatients were admitted (median-6 days), primarily for progressing infection. Thus 92% of all transplant days were outpatient. There were no septic episodes or hospital admissions for pain management. There were no deaths to day 30 in either group and 100-day survival was identical. There was a mean cost savings of Dollars 16,000 per outpatient transplant and outpatient patient/caregiver quality of life was similar to that reported for in-patients. Patients undergoing severely mucotoxic regimens can be safely transplanted in an outpatient setting with a significant cost saving, with no increase in morbidity or mortality.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Outpatients , Whole-Body Irradiation/methods , Adult , Cost Savings , Female , Follow-Up Studies , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/economics , Humans , Kaplan-Meier Estimate , Male , Pain/etiology , Pain Management , Patient Admission/economics , Patient Admission/statistics & numerical data , Quality of Life , Transplantation, Autologous , Whole-Body Irradiation/adverse effects
15.
Bone Marrow Transplant ; 38(10): 693-8, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16980989

ABSTRACT

Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is thought to be the procedure of choice to evaluate pulmonary infiltrates in hematopoietic stem cell transplant (HSCT) recipients. We retrospectively reviewed 91 bronchoscopies performed on 190 in-patient HSCT recipients admitted or treated for pneumonia from January 1994 to December 2004. These yielded a diagnosis 49% of the time with an overall survival of 35 days post-bronchoscopy. We were unable to detect any survival benefit from an addition to the treatment regimen after a positive result from analysis of the BAL fluid or transbronchial biopsy. The most common bacteria isolated was Pseudomonas that was often resistant to the patient's current antibiotics, suggesting that in lieu of this diagnostic procedure, changes to better cover resistant Gram-negative bacteria are reasonable. Although transbronchial biopsies provided an additional diagnosis in one out of 21 biopsies performed, six of the seven complications in our series were directly related to the transbronchial biopsy. With approximately a 50% yield from a bronchoscopy, additional treatment given after only 20% of all bronchoscopies, and no detectable survival benefit with a bronchoscopy that yielded a diagnosis, the utility of a bronchoscopy in this patient population is questioned by these data.


Subject(s)
Bronchoscopy , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Aged , Bronchoalveolar Lavage Fluid/microbiology , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/etiology , Pseudomonas Infections/diagnosis , Pseudomonas Infections/etiology , Retrospective Studies
16.
Ann Oncol ; 17(6): 897-907, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16547070

ABSTRACT

Intravenous bisphosphonates are widely used to treat hypercalcemia and to reduce skeletal-related morbidity among cancer patients. However, serious complications, generally occurring in less than 2% of patients participated in phase III clinical trials, including acute systemic inflammatory reaction, ocular inflammation, renal failure, nephrotic syndrome, electrolyte imbalance, and osteonecrosis of the maxilla and mandible have all been increasingly reported. Yet, strategies to deal with these complications are becoming clear. Acute systemic inflammatory reaction is often self-limited and becomes less intense during subsequent treatments. For patients who develop ocular symptoms, prompt ophthalmologic evaluation is crucial to determine the safety of a subsequent bisphosphonate therapy. Patients who receive long-term pamidronate should be evaluated at intervals for early sign of nephritic syndrome as timely cessation of the agent may result in a full recovery. To reduce the risk of severe electrolyte abnormalities, particularly hypocalcemia, correcting any pre-treatment electrolyte abnormality and supplementing vitamin D and calcium may be helpful. Finally, to reduce the risk of osteonecrosis of the maxilla and mandible, obtaining a full dental evaluation before treatment and avoidance of invasive dental procedures is suggested. The three commonly used intravenous bisphosphonates (pamidronate, zoledronic acid, and ibandronate), are generally safe; ibandronate has to date been the least reported to be associated with renal side effects. As clinical indications of intravenous bisphosphonates continue to expand, prescribing clinicians should be familiar with these possible adverse effects and discuss them with patients before commencing or continuing on therapy.


Subject(s)
Antineoplastic Agents/adverse effects , Diphosphonates/adverse effects , Antineoplastic Agents/therapeutic use , Bone Density Conservation Agents/adverse effects , Diphosphonates/administration & dosage , Humans , Imidazoles/adverse effects , Inflammation , Infusions, Intravenous/adverse effects , Osteoclasts/cytology , Osteoclasts/drug effects , Osteoclasts/pathology , Osteoclasts/physiology , Pamidronate , Zoledronic Acid
17.
Bone Marrow Transplant ; 37(5): 479-84, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16435021

ABSTRACT

Patients referred for hematopoietic stem cell transplantation (HSCT) often have knowledge deficits about their disease and overestimate their prognosis making it difficult initially to discuss potentially life-threatening transplant options. To determine patients' understanding of their disease and the adequacy of a 3-h consultation at our center, we developed a survey that measured perceived knowledge deficits of disease, prognosis, and emotional status before and after their initial consultation. Ninety nine consecutive eligible patients completed the survey. Although 76.7% claimed adequate information about their disease pre-HCST visit, 51.5 and 41.4% respectively lacked knowledge about their 1-year prognosis with and without any therapy. After the visit, 66.7% of the patients had obtained enough information to make an informed decision regarding HSCT versus 23.2% pre-visit, and a significant reduction in the need for further information was reported by 53.5% of patients (P<0.001). Patients were not overwhelmed or confused by the visit and there was a small but significant decrease in negative affect. Measures to increase patients understanding of their disease and its prognosis pre-HSCT consultation visit are warranted; however, a 3-h consultation visit provides the majority of patients with sufficient information to make an informed decision about the risk/benefit ratio of HSCT.


Subject(s)
Hematologic Diseases , Hematopoietic Stem Cell Transplantation , Patient Education as Topic/standards , Referral and Consultation/standards , Data Collection , Decision Making , Health Status , Humans , Informed Consent/standards , Prognosis , Risk Assessment
18.
Bone Marrow Transplant ; 37(4): 393-401, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16415901

ABSTRACT

Oral mucositis (OM) is a frequent complication of myeloablative therapy and HSCT. We evaluated the feasibility, reliability, and validity of a new patient self-reported daily questionnaire on OM and its impact on daily functions. This OM Daily Questionnaire (OMDQ), containing 10 items, was developed for use in palifermin clinical trials. In a phase 3 study, 212 patients received palifermin or placebo for three consecutive days before conditioning and three consecutive days after HSCT. Compliance rates were consistently >80% for most patients. Mouth and throat soreness (MTS) and MTS-Activity Limitations (MTS-AL) (swallowing, drinking, eating, talking, and sleeping) scores on consecutive days were highly correlated (days 7,8 = 0.70-0.86; test-retest reliability). Correlations among items measuring the same construct ranged between 0.5 and 0.8 (internal consistency reliability). The WHO Oral Toxicity scale was the clinical comparator to assess the criterion, discriminative, and evaluative validities of MTS-related questions. Most correlation coefficients between the WHO and MTS ranged between 0.45 and 0.55. Patients with more severe WHO OM grades had higher MTS mean scores. Changes in MTS scores were similar, but patients detected changes 1-3 days earlier than clinicians. In conclusion, the OMDQ is a feasible, reliable, valid, and responsive patient-reported measure of OM severity.


Subject(s)
Activities of Daily Living , Hematopoietic Stem Cell Transplantation , Pain/diagnosis , Stomatitis/physiopathology , Surveys and Questionnaires , Adolescent , Adult , Aged , Double-Blind Method , Feasibility Studies , Female , Fibroblast Growth Factor 7/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Pain/etiology , Patient Compliance , Placebos , Reproducibility of Results , Stomatitis/complications , Stomatitis/drug therapy , Transplantation, Autologous
19.
Bone Marrow Transplant ; 35(3): 261-4, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15558039

ABSTRACT

A second allogeneic hematopoietic stem cell transplant (HSCT) for relapsed hematologic malignancies is an option in select patients after an initial allograft has failed. If the original donor is not available, a different donor may have to be considered. We report our experience of performing a second allogeneic HSCT using a different donor in patients with relapsed leukemia and lymphoma. In a 5-year period, six patients underwent a second allograft with myeloablative conditioning using a different donor. Four of these were retransplanted using a matched-unrelated donor. Four of the patients (67%) remain progression-free at a median follow-up of 32 months (range 3-72). There were no cases of transplant-related mortality. We conclude that a second allogeneic HSCT using a different donor is a viable option for selected patients relapsing after an allograft if the original donor is not available.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Salvage Therapy/methods , Tissue Donors , Adolescent , Adult , Disease-Free Survival , Feasibility Studies , Female , Graft Survival , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation/adverse effects , Histocompatibility , Humans , Incidence , Leukemia/therapy , Lymphoma/therapy , Male , Middle Aged , Retrospective Studies , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods , Transplantation, Homologous
20.
Bone Marrow Transplant ; 33(10): 997-1003, 2004 May.
Article in English | MEDLINE | ID: mdl-15064690

ABSTRACT

Inadequate stem cell mobilization is seen in approximately 25% of patients undergoing autotransplantation for hematologic malignancies. Remobilization strategies include chemotherapy/cytokine combinations or high-dose cytokines alone or in combination. From 1/1997 to 7/2002, we remobilized 86 patients who failed an initial mobilization (median total CD34=0.72 x 10(6)/kg) in sequential cohorts using high-dose G-CSF (32 microg/kg/day) or G-CSF(10 microg/kg/day)+GM-CSF (5 microg/kg/day). No difference in CD34/kg yields were seen (G-CSF alone: 2.2 x 10(6) and G-CSF+GM-CSF 1.6 x 10(6)) in the median 3 aphereses performed (P=0.333). Of the 86, 23 (27%) failed the second mobilization; 14 were remobilized again (yield=1.5 x 10(6) CD34/kg; three aphereses). Of the 86, 93% went to transplant: three progressed, and three had inadequate stem cells. Significant risk factors for a failed remobilization were: number of stem-cell-damaging regimens (P=0.015), time between last chemotherapy and first mobilization (P=0.028), and higher WBC at initiation of first mobilization (P=0.04). High-dose G-CSF (32 microg/kg/day) was more costly @ USD $9,016, vs $5,907 for the G-CSF+GM-CSF combination (P<0.001). Most patients failing an initial mobilization benefit from a cytokine only remobilization. Lower cost G-CSF+GM-CSF is as effective as high-dose G-CSF.


Subject(s)
Cytokines/therapeutic use , Neoplasms/therapy , Stem Cell Transplantation/methods , Transplantation, Autologous/methods , Adult , Aged , Antigens, CD34/biosynthesis , Blood Component Removal , Cohort Studies , Cytokines/biosynthesis , Female , Granulocyte Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Hematopoietic Stem Cell Mobilization/economics , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Stem Cell Transplantation/economics , Transplantation Conditioning/economics , Transplantation, Autologous/economics
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