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1.
Ann Oncol ; 22(7): 1608-1613, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21252059

ABSTRACT

BACKGROUND: The prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome. PATIENTS AND METHODS: This study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other. RESULTS: Median follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients. CONCLUSION: Allogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.


Subject(s)
Graft vs Host Disease/etiology , Lymphoma, T-Cell, Peripheral/therapy , Mycosis Fungoides/therapy , Sezary Syndrome/therapy , Skin Neoplasms/therapy , Stem Cell Transplantation , Adult , Aged , Female , Follow-Up Studies , Graft vs Host Disease/therapy , Humans , Lymphoma, T-Cell, Peripheral/complications , Male , Middle Aged , Mycosis Fungoides/complications , Sezary Syndrome/complications , Skin Neoplasms/complications , Survival Rate , Transplantation, Homologous , Treatment Outcome , Young Adult
2.
J Exp Med ; 161(6): 1483-502, 1985 Jun 01.
Article in English | MEDLINE | ID: mdl-3159819

ABSTRACT

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell-depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu-2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Bone Marrow Transplantation , Lymphocytes/immunology , Adolescent , Adult , Antigens, Differentiation, T-Lymphocyte , Antigens, Surface/immunology , B-Lymphocytes/immunology , Cell Count , Child, Preschool , DNA/genetics , Female , Humans , Killer Cells, Natural/immunology , Leukemia/therapy , Lymphocytes/classification , Male , Phenotype , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology
3.
Eur J Cancer Care (Engl) ; 18(1): 57-63, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19473223

ABSTRACT

The purpose of this study of 23 adult haematopoietic stem cell transplantation (HSCT) recipients is to compare the presence of post-transplantation depression disorders by gender and to compare the outcomes among those with and without depressive disorders using a health psychology focus. This cross-sectional pilot study of mid-term survivors took place in hospital outpatient clinic. Main outcome measures are depression disorders, health status (Short Form-12) and health anxiety. Female survivors had a higher rate of depression disorders, but those with treated depressive disorders were similar to those without depression on health-related quality of life and health anxiety. Neither patient age nor time since HSCT was associated with depressive disorders. A health psychology approach may enhance management of HSCT survivorship.


Subject(s)
Depressive Disorder/psychology , Hematopoietic Stem Cell Transplantation/psychology , Neoplasms/therapy , Quality of Life/psychology , Adult , Age Factors , Aged , Aged, 80 and over , Cross-Sectional Studies , Depressive Disorder/etiology , Female , Health Status , Humans , Male , Middle Aged , Pilot Projects , Sex Factors , Stress, Psychological/psychology , Time Factors , Young Adult
5.
Bone Marrow Transplant ; 41(6): 523-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18037942

ABSTRACT

Double cord blood transplantation (DCBT) may overcome the slow hematopoietic recovery and engraftment failure associated with infusion of a single cord blood unit. In DCBT, only one unit typically contributes to long-term hematopoiesis, but little is known about factors affecting cord predominance. As results from a phase I trial suggested that order of infusion may affect cord predominance, we analyzed the effect of preinfusion variables on chimerism patterns of 38 patients enrolled in the initial study and a subsequent phase II trial. All patients were treated with a reduced-intensity conditioning (RIC) regimen of fludarabine, melphalan and thymoglobulin followed by DCBT. By day 100, 66% of patients had hematopoiesis derived from a single cord blood unit. Higher post-thaw total nucleated cell and CD34+ cell dose were associated with cord predominance and in 68% of patients (P=0.03); the predominant cord blood unit was infused first. Only the post-thaw CD34+ cell dose of the predominant unit predicted time to both neutrophil and platelet engraftment. Although based on a small number of patients, our results identify parameters that may affect cord predominance and engraftment in the setting of DCBT following RIC and suggest possible strategies for selecting infusion order for cord blood units.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft Survival , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Erythroblasts/transplantation , Female , Humans , Immunosuppressive Agents/administration & dosage , Macrocyclic Compounds/administration & dosage , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Predictive Value of Tests , Receptors, Complement 3b/metabolism , Time Factors , Transplantation Chimera
6.
Bone Marrow Transplant ; 53(1): 64-68, 2018 01.
Article in English | MEDLINE | ID: mdl-29058696

ABSTRACT

Follistatin is an angiogenic factor elevated in the circulation after allogeneic hematopoietic cell transplantation (HCT). Elevations in follistatin plasma concentrations are associated with the onset of and poor survival after acute GvHD (aGvHD). Using data from the Blood and Marrow Transplant Clinical Trials Network 0402 study (n=247), we sought to further quantify the longitudinal associations between plasma follistatin levels in transplant recipients, as well as baseline HCT donor follistatin levels, and allogeneic HCT outcomes. Higher recipient baseline follistatin levels were predictive of development of aGvHD (P=0.04). High donor follistatin levels were also associated with the incidence of aGvHD (P<0.01). Elevated follistatin levels on day 28 were associated with the onset of grade II-IV aGvHD before day 28, higher 1-year non-relapse mortality (NRM) and lower overall survival. In multivariate analyses, individuals with follistatin levels >1088 pg/mL at day 28 had a 4-fold increased risk for NRM (relative risk (RR)=4.3, 95% confidence interval (CI) 1.9-9.9, P<0.01) and a nearly three-fold increased overall risk for mortality (RR=2.8, 95% CI 1.5-5.2, P<0.01). Given the multiple roles of follistatin in tissue inflammation and repair, and the confirmation that this biomarker is predictive of important HCT outcomes, the pathobiology of these relationships need further study.


Subject(s)
Follistatin/adverse effects , Graft vs Host Disease/etiology , Acute Disease , Adolescent , Adult , Child , Female , Graft vs Host Disease/pathology , Humans , Male , Middle Aged , Tissue Donors , Young Adult
7.
J Clin Invest ; 80(2): 325-32, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3112184

ABSTRACT

Differences in the expression of Leu-1 (CD5) define two populations of recovering B cells after human marrow transplantation, Leu-1+ and Leu-1- B cells. The Leu-1+ B cells were polyclonal, of donor origin, and did not express detectable interleukin 2 receptor. Leu-1+ B cells generally appeared 2-4 wk after marrow grafting and often preceded the recovery of Leu-1- B cells. Acute and chronic graft vs. host disease (GvHD) resulted in the recovery of significantly fewer Leu-1+ B cells, whereas Leu-1- B cells were only decreased in acute GvHD. Multivariate analysis showed no significant effect of age, disease, prednisone or azathioprine, or ex vivo treatment of the marrow with anti-Leu-1 and complement on recovery of Leu-1+ and Leu-1- B cells, independent of the effects of GvHD. Leu-1+ B cells are a major lymphocyte population posttransplant. They may reflect a stage of differentiation of normal B cells or a separate B cell lineage.


Subject(s)
Antigens, Surface/analysis , B-Lymphocytes/cytology , Bone Marrow Transplantation , Antibody Formation , Antigens, Differentiation, B-Lymphocyte , Cell Differentiation , Flow Cytometry , Graft vs Host Disease/immunology , Humans , Immunoglobulin G/analysis , Time Factors
8.
J Clin Invest ; 75(2): 596-603, 1985 Feb.
Article in English | MEDLINE | ID: mdl-3882761

ABSTRACT

After successful bone marrow transplantation, patient hematopoietic and lymphoid cells are replaced by cells derived from the donor marrow. To document and characterize successful engraftment, host and donor cells must be distinguished from each other. We have used DNA sequence polymorphism analysis to determine reliably the host or donor origin of posttransplant cell populations. Using a selected panel of six cloned DNA probes and associated sequence polymorphisms, at least one marker capable of distinguishing between a patient and his sibling donor can be detected in over 95% of cases. Posttransplant patient peripheral leukocytes were examined by DNA restriction enzyme digestion and blot hybridization analysis. We have studied 18 patients at times varying from 13 to 1,365 d after marrow transplantation. Mixed lymphohematopoietic chimerism was detected in 3 patients, with full engraftment documented in 15. One patient with severe combined immunodeficiency syndrome was demonstrated to have T cells of purely donor origin, with granulocytes and B cells remaining of host origin. Posttransplant leukemic relapse was studied in one patient and shown to be of host origin. DNA analysis was of particular clinical value in three cases where failure of engraftment or graft loss was suspected. In two of the three cases, full engraftment was demonstrated and in the third mixed lymphohematopoietic chimerism was detected. DNA sequence polymorphism analysis provides a powerful tool for the documentation of engraftment after bone marrow transplantation, for the evaluation of posttransplant lymphoma or leukemic relapse, and for the comprehensive study of mixed hematopoietic and lymphoid chimeric states.


Subject(s)
Bone Marrow Transplantation , DNA/genetics , Adult , Base Sequence , Child , Chimera , Cloning, Molecular , Female , Graft Rejection , Hematopoietic System/metabolism , Humans , Infant , Lymphoid Tissue/metabolism , Male , Polymorphism, Genetic
9.
Bone Marrow Transplant ; 40(3): 209-17, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17563734

ABSTRACT

We compared inpatient and outpatient costs alongside clinical outcomes associated with hematopoietic cell transplantation between 2000 and 2003 with high-dose regimens (HDCT, n=185) and with reduced intensity regimens (RICT, n=90) from human leukocyte antigen (HLA)-matched donors for patients with hematological malignancies. With a comparable median follow-up of 3 years, long-term clinical outcomes, including cumulative incidence of chronic graft-vs-host disease, disease-free survival and overall survival, were similar between the two groups. In the univariate analysis, median costs for the first 100 days ($104,380 vs $42,149) and 1 year ($128,253 vs $80,499) in the HDCT group were higher than those in the RICT group. Median days of hospitalization are also higher for HDCT recipients (39 vs 21), although the number of outpatient clinic visits for HDCT recipients were fewer compared to that for RICT recipients (16 vs 25) during the first year. Adjusting for patient characteristics, RICT recipients had approximately 16 fewer days of hospitalization and cost $53,030 less than HDCT recipients within the first year after transplantation. Our data suggest that substantially lower costs and fewer days of hospitalization within the first year after RICT procedures can be obtained with no compromise of long-term clinical outcomes compared to HDCT procedures.


Subject(s)
Ambulatory Care/economics , Hematologic Neoplasms/economics , Hematopoietic Stem Cell Transplantation/economics , Length of Stay/economics , Adolescent , Adult , Aged , Child , Costs and Cost Analysis , Disease-Free Survival , Female , Follow-Up Studies , Graft vs Host Disease/economics , Graft vs Host Disease/mortality , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/mortality , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Survival Rate
10.
Bone Marrow Transplant ; 52(9): 1300-1303, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28581470

ABSTRACT

Epidermal growth factor (EGF) is a recently described biomarker of acute GvHD (aGvHD). Whether low plasma EGF prior to hematopoietic cell transplantation (HCT) predisposes to the development of aGvHD, or whether EGF levels fall because of severe aGvHD, is unknown. To evaluate this, we tested plasma samples collected at pre-HCT baseline, day +28 and day +100 during the course of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. We found that baseline EGF plasma concentrations were three-fold lower in HCT recipients compared to donors (24.3 vs 76.0 pg/mL, P<0.01). Ninety-one patients (43%) had a markedly low plasma EGF at pre-HCT baseline, defined as <2.7 pg/mL-an optimal cutpoint associated with development of grade III-IV aGvHD. Patients with these low EGF levels at pre-HCT baseline had a 2.9-fold increased risk of grade III-IV aGvHD by day +100. Patients with low EGF at day +28 after HCT had an increased risk of death (relative risk 2.3, P=0.02) by 1 year due to transplant-related toxicities, especially aGvHD. Our results suggest that very low plasma EGF early in the HCT process may predispose patients to an increased risk of death, potentially due to epithelial damage and limited repair capacity.


Subject(s)
Bone Marrow Transplantation/adverse effects , Epidermal Growth Factor/metabolism , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Vascularized Composite Allotransplantation/methods , Adult , Female , Humans , Male , Middle Aged
11.
Bone Marrow Transplant ; 37(9): 845-50, 2006 May.
Article in English | MEDLINE | ID: mdl-16532020

ABSTRACT

HLA-C matching is an important determinant of outcome after myeloablative unrelated donor (URD) hematopoietic stem cell transplantation. However, its importance in non-myeloablative stem cell transplantation (NST) is not known. We report a retrospective analysis of 111 patients who underwent URD NST, of whom 78 were 10/10 matched at HLA-A, B, C, DRB1, DQB1 and 33 were mismatched at one or more HLA-C antigen/allele (24 HLA-C only; nine HLA-C+other locus mismatch). Patients were conditioned with busulfan (0.8 mg/kg/day i.v. x 4 days) and fludarabine (30 mg/m(2)/day i.v. x 4 days). Graft-versus-host disease prophylaxis included cyclosporine/prednisone- or tacrolimus/mini-methotrexate-based regimens. HLA-C disparity did not impair engraftment. Median marrow donor chimerisms were >or=90% donor at day+30 and +100 in both groups. Overall survival at 2 years was 30% in HLA-C-mismatched and 51% in 10/10-matched patients (P=0.008). In Cox regression, HLA-C mismatch was an independent predictor of death (hazard ratio 1.85, P=0.04). Treatment-related mortality was higher in the HLA-C-mismatched group: 48 versus 16% (P=0.0001). Cumulative relapse incidence was 35% in the HLA-C-mismatched and 55% in the 10/10-matched cohort, P=0.09. HLA-C mismatch is associated with inferior survival after URD NST.


Subject(s)
HLA-C Antigens/immunology , Hematologic Neoplasms/therapy , Stem Cell Transplantation/methods , Adolescent , Adult , Aged , Female , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Histocompatibility Testing , Humans , Major Histocompatibility Complex , Male , Middle Aged , Recurrence , Retrospective Studies , Stem Cell Transplantation/mortality , Survival Analysis , Tissue Donors/statistics & numerical data , Treatment Outcome
12.
Bone Marrow Transplant ; 38(4): 305-10, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16819438

ABSTRACT

Acute and chronic graft-versus-host diseases (GVHD) are associated with increased morbidity and mortality after hematopoietic stem cell transplantation (HCT). We prospectively measured the quality of life (QOL) of patients undergoing allogeneic transplantation. Ninety-six subjects completed self-assessment surveys before HCT, and at 6 and/or 12 months post-HCT that included the Medical Outcomes Study Short Form 12 (SF12) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale. Eighty-three percent of survivors responded at 6 and 12 months. Physical and mental functioning assessed by the SF12 was not associated with either acute or chronic GVHD. In contrast, the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant was sensitive to occurrence of either acute or chronic GVHD. GVHD is a major determinant of the long-term QOL of survivors. The adverse effects of acute GVHD are detectable with the TOI at 6 months post transplantation after which development of chronic GVHD is the most strongly correlated with worse QOL.


Subject(s)
Graft vs Host Disease , Quality of Life , Acute Disease , Adult , Aged , Chronic Disease , Data Collection , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Prospective Studies , Self-Assessment , Time Factors
13.
J Clin Oncol ; 18(1): 64-71, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10623694

ABSTRACT

PURPOSE: Few studies have formally evaluated the relationship between costs, baseline patient characteristics, and major complications of stem-cell transplantation. We sought (1) to determine whether obtaining baseline information enabled identification of patients whose treatments would be the most costly and (2) to estimate inpatient costs for managing specific transplantation complications. PATIENTS AND METHODS: We collected inpatient costs and clinical information for 236 consecutive patients undergoing transplantation at a single institution between July 1, 1994, and February 20, 1997. Multivariable linear regression was used to evaluate the associations between baseline patient characteristics and costs of hospitalization for initial transplantation and between clinical events and such costs. RESULTS: The median initial inpatient cost in 1997 dollars was $55,500 for autologous transplantation (range, $28,200 to $148,200) and $105,300 for allogeneic transplantation (range, $32,500 to $338,000). When only baseline variables were considered, use of a mismatched allogeneic donor and year of transplantation were significant predictors of costs. No characteristics predicted which patients would incur the highest 10% of costs. When clinical events were considered, infection and in-hospital death were associated with higher costs in autologous transplant recipients ($18,400 and $20,500, respectively), whereas infection, veno-occlusive disease, acute graft-versus-host disease, and death were predicted to add between $15,300 and $28,100 each to allogeneic transplantation costs. CONCLUSION: We were not able to identify before transplantation the patients whose treatments would be the most costly. However, the association between clinical complications and higher costs suggests that prevention may have significant economic benefits. Interventions that decrease these complications may have favorable cost-benefit ratios even if they do not affect overall survival.


Subject(s)
Health Care Costs , Hematopoietic Stem Cell Transplantation/economics , Risk Adjustment/economics , Adolescent , Adult , Cost-Benefit Analysis , Female , Graft vs Host Disease/economics , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Massachusetts , Middle Aged , Models, Econometric , Regression Analysis , Risk Factors , Transplantation Conditioning/economics , Transplantation, Autologous , Transplantation, Homologous
14.
J Clin Oncol ; 16(9): 2897-903, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9738555

ABSTRACT

For patients with newly diagnosed CML, the life expectancy is much better than it was 5 years ago. However, with improvements in both transplant and nontransplant therapy comes controversy over optimal first-line therapy. We argue that an evidence-based analysis that weighs the likelihoods of surviving transplantation and responding to interferon should help guide selection of initial therapy. Such a strategy would aggressively triage appropriate patients to curative therapy while advising those who are unlikely to do well with transplantation to elect less toxic therapy, which still confers a survival benefit. We realize that many other factors beside the ones mentioned here affect a clinician's recommendation for initial therapy and a patient's ultimate choice. Many extenuating circumstances, coexisting medical conditions, and personal values need to be a part of the ultimate decision. However, we hope that this guideline summarizes the current evidence and offers a rational approach to help guide newly diagnosed patients.


Subject(s)
Bone Marrow Transplantation , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adult , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Middle Aged
15.
J Clin Oncol ; 8(10): 1707-14, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2213106

ABSTRACT

Twenty-three patients with primary myelodysplasia (MDS) or secondary myelodysplasia/acute nonlymphocytic leukemia (MDS/ANLL) were treated with allogeneic or syngeneic bone marrow transplantation (BMT). Only one patient was in a chemotherapy-induced hematologic remission. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, cyclosporine, or T-cell depletion using one of two anti-CD5 monoclonal antibodies. For patients with primary MDS, the median age was 19 years (range, 11 to 41 years) and the actuarial disease-free survival was 56% +/- 21% (median follow-up, 2 years; range, 0.8 to 5 years). There were three graft failures (two with autologous recovery) and two early deaths. Outcome appeared to be related to French-American-British (FAB) classification. For patients with secondary MDS/ANLL, the median age was 28 years (range, 3 to 16 years) and the actuarial disease-free survival was 27% +/- 13% (median follow-up, 5 years; range, 2.5 to 8.5 years). There were no graft failures, two relapses, and four early deaths. The presence of marrow fibrosis per se did not predict for graft failure (P = .21); however, the use of T-cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals. Our results suggest that in patients with primary MDS or secondary MDS/ANLL, BMT should be considered early in the course of the disease, and that attempts at inducing a remission prior to BMT appeared to be unnecessary. In MDS patients with marrow fibrosis, T-cell depletion should be avoided.


Subject(s)
Bone Marrow Transplantation , Leukemia, Myeloid, Acute/surgery , Myelodysplastic Syndromes/surgery , Actuarial Analysis , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Evaluation Studies as Topic , Female , Graft Survival , Humans , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/mortality , Leukemia, Radiation-Induced/etiology , Leukemia, Radiation-Induced/mortality , Leukemia, Radiation-Induced/surgery , Lymphocyte Depletion , Male , Middle Aged , Myelodysplastic Syndromes/etiology , Myelodysplastic Syndromes/mortality , Primary Myelofibrosis/complications , Radiation Injuries/etiology , Radiation Injuries/mortality , Radiation Injuries/surgery , Radiotherapy/adverse effects , Survival Rate , T-Lymphocytes
16.
J Clin Oncol ; 19(16): 3685-91, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11504750

ABSTRACT

PURPOSE: Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. METHODS: An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. RESULTS: Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P=.006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P <.001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P <.001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). CONCLUSION: Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.


Subject(s)
Bone Marrow Transplantation/adverse effects , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia/therapy , Acute Disease , Case-Control Studies , Chronic Disease , Cohort Studies , Humans , Randomized Controlled Trials as Topic , Risk Factors
17.
J Clin Oncol ; 9(7): 1215-23, 1991 Jul.
Article in English | MEDLINE | ID: mdl-2045862

ABSTRACT

Cyclophosphamide (CY) cardiotoxicity may be a lethal complication of bone marrow transplantation. Previous echocardiographic studies have reported that left ventricular dysfunction due to CY occurs in over 50% of patients undergoing transplantation. To evaluate the cardiotoxicity of new dosing protocols that included twice-daily rather than once-daily CY, 44 bone marrow transplantation patients were prospectively evaluated with serial ECGs and echocardiograms. Twenty-six patients received a once-daily lower-dose protocol (mean total 87 +/- 11 mg/kg), and 18 patients received a twice-daily higher-dose (mean total 174 +/- 34 mg/kg) CY regimen. In the higher-dose CY group, significant reductions in summed ECG voltage (-20%) (P less than .01) and increases in left ventricular mass index (LVMI) (+10%) (P less than .05) were detected in the first week following therapy. These changes resolved by the third week following CY and were significantly greater than the changes noted in the lower-dose group. However, left ventricular ejection fraction (EF) did not change significantly in either group. Five patients developed clinical cardiotoxicity (four, pericarditis; one, congestive heart failure); four of the five patients were in the higher-dose group (P = .14). Only a prior history of congestive heart failure or a baseline EF less than 50% was an independent correlate of clinical cardiotoxicity (P less than .05). Thus, dose-dependent cardiotoxicity following the use of CY for bone marrow transplantation is evident as reversible decreases in ECG voltage and increases in left ventricular mass, possibly reflecting myocardial edema or hemorrhage. However, systolic dysfunction is much less common with these new twice-daily dosing regimens when compared with earlier studies of high-dose once-daily CY.


Subject(s)
Bone Marrow Transplantation , Cyclophosphamide/adverse effects , Heart Failure/chemically induced , Pericarditis/chemically induced , Adult , Aged , Analysis of Variance , Cyclophosphamide/administration & dosage , Drug Administration Schedule , Echocardiography/drug effects , Electrocardiography/drug effects , Evaluation Studies as Topic , Female , Humans , Male , Middle Aged , Prospective Studies , Regression Analysis , Ventricular Function, Left/drug effects
18.
J Clin Oncol ; 8(10): 1699-706, 1990 Oct.
Article in English | MEDLINE | ID: mdl-2213105

ABSTRACT

Retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation (BMT) was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease (VOD). Twelve patients (4.1%) developed a clinical syndrome of right upper quadrant (RUQ) tenderness or hepatomegaly, jaundice, and ascites, with or without encephalopathy, within 40 days of marrow reinfusion. Evidence of metastatic liver disease was the only pretransplant characteristic predictive for VOD (P = .0002). Sex, age, histology, hepatitis B serology, and elevated liver function tests were not predictive. No individual preparative agent had a significant effect on the development of VOD. However, a single 2-hour infusion of carmustine (BCNU) (greater than or equal to 450 mg/m2) led to an increased incidence of VOD when compared with the same dose administered in a fractionated schedule (P = .0258) when given with two other chemotherapeutic agents. Seven of eight autopsy specimens confirmed the clinical diagnosis of VOD. The four patients in whom clinical VOD resolved had lower median peak bilirubins (7.3 v 15.9 mg/dL), lower median peak creatinines (2.1 v 4.1 mg/dL), and relatively quick engraftment of neutrophils (mean, 18.7 days). One of the four patients in whom VOD resolved had other grade 4 (life-threatening) toxicities in contrast to eight of eight who succumbed. In summary, VOD is an uncommon complication in autotransplantation of solid tumors and lymphomas. Our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated BCNU schedule especially in combination with other alkylating agents.


Subject(s)
Bone Marrow Transplantation/adverse effects , Hepatic Veno-Occlusive Disease/etiology , Lymphoma/surgery , Neoplasms/surgery , Adult , Carmustine/administration & dosage , Carmustine/adverse effects , Combined Modality Therapy , Female , Humans , Liver Neoplasms/secondary , Lymphoma/drug therapy , Male , Middle Aged , Neoplasms/drug therapy , Prognosis , Retrospective Studies , Risk Factors
19.
J Clin Oncol ; 11(5): 937-42, 1993 May.
Article in English | MEDLINE | ID: mdl-8387578

ABSTRACT

PURPOSE: A study was undertaken to improve our understanding of the clinicopathologic features and therapeutic outcome for adults with primary Ki-1 anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS: A retrospective review of records of 31 adult patients with primary Ki-1 ALCL was performed. The analysis included stage and distribution of disease, tumor-cell phenotype, response to initial and salvage therapy, and disease-free and overall survival. RESULTS: The median age of patients was 44 years (range, 16 to 86). Forty-eight percent of patients tested had lymphomas of T-cell phenotype, 30% lymphomas of B-cell phenotype, and 22% of non-T-, non-B-cell phenotype. Twenty-nine percent of patients had stages I and II disease, 65% demonstrated extranodal involvement, and 32% had skin involvement at presentation. Most patients received intensive chemotherapy and 48% achieved a sustained complete remission (CR), with an additional 17% of patients treated successfully with salvage therapy. Stage was highly predictive of achieving a sustained CR, but bulk disease and B symptoms did not predict for relapse after initial therapy or survival. Of seven patients who underwent autologous bone marrow transplantation (ABMT), three remain disease-free 9 to 42 months after transplant. CONCLUSION: Patients with Ki-1 ALCL have a high frequency of advanced-stage disease and extranodal involvement and are more likely to have tumors of T-cell phenotype than patients with large-cell lymphoma. However, response to standard lymphoma chemotherapy is similar to other patients with large-cell lymphoma, with a high remission rate in early-stage disease. Patients with advanced-stage disease have a poor remission duration and may require more intensive therapy, as may also be the case with large-cell lymphoma.


Subject(s)
Antigens, CD/analysis , Antigens, Neoplasm/analysis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Follow-Up Studies , Humans , Ki-1 Antigen , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Staging , Outcome Assessment, Health Care , Phenotype , Retrospective Studies , Salvage Therapy
20.
J Clin Oncol ; 19(1): 242-52, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11134219

ABSTRACT

PURPOSE: Although the number of autologous and allogeneic stem-cell transplantations (SCT) is increasing, relatively little information about recovery after transplantation is available. Quantitative information appropriate for patient counseling is difficult to discern from the literature. We sought to suggest reasonable expectations for recovery and symptoms after SCT for hematologic malignancies and other disorders using the following measures: (1) objective measures of health status, such as frequency of clinic visits, need for rehospitalization, medication usage, work status, and overall and event-free survival; (2) qualitative assessment of quality of life, such as returning to a normal life, resumption of normal activities, satisfaction with appearance, and whether recovery has occurred; and (3) quantification of specific bothersome symptoms. PATIENTS AND METHODS: Autologous and allogeneic SCT recipients at a tertiary-care transplant center participated in the prospective, longitudinal questionnaire study. RESULTS: Three hundred twenty patients were studied. Questionnaire response rates at 6, 12, and 24 months range from 85% to 88% among survivors. Although autologous patients had better event-free and overall survival, fewer symptoms, and more complete recovery at 6 months, these advantages had largely equalized by 12 months. Specific bothersome symptoms were reported by less than 24% of patients after transplantation, except for fatigue and financial and sexual difficulties, which were more prevalent. CONCLUSION: These findings may help counsel patients considering transplantation and educate them about reasonable expectations for recovery. Overall, the low level of bothersome symptoms and continued recovery through the first year after transplantation are encouraging.


Subject(s)
Hematologic Diseases/rehabilitation , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation , Recovery of Function , Activities of Daily Living , Adult , Aged , Disease-Free Survival , Female , Health Status , Hematologic Diseases/mortality , Humans , Logistic Models , Male , Middle Aged , Prospective Studies , Quality of Life , Statistics, Nonparametric , Survival Rate , Transplantation, Autologous , Transplantation, Homologous , Treatment Outcome , United States/epidemiology
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