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1.
Aust Dent J ; 60(4): 532-5, 2015 12.
Article in English | MEDLINE | ID: mdl-25484130

ABSTRACT

A brain abscess that originates from an odontogenic infection, although rare, can at times be difficult to diagnose, especially in the context of pain and trismus. We report a rare case of odontogenic infection as a result of an infected maxillary third molar, causing an infratemporal and temporalis collection, resulting in a brain abscess with concurrent cerebritis. This is a clinical case review documenting an uncommon but potentially fatal complication.


Subject(s)
Brain Abscess/etiology , Focal Infection, Dental/complications , Tooth Diseases/complications , Adult , Anti-Bacterial Agents/therapeutic use , Brain Abscess/diagnostic imaging , Brain Abscess/drug therapy , Focal Infection, Dental/diagnostic imaging , Focal Infection, Dental/drug therapy , Humans , Male , Tomography, X-Ray Computed , Tooth Diseases/diagnostic imaging , Tooth Diseases/drug therapy
2.
Aust Dent J ; 58(3): 373-5, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23981222

ABSTRACT

The manifestation of metastatic malignant disease in the oral cavity can present in a number of ways and may mimic benign conditions. This case reports a rare presentation from a metastasis of a hepatocellular carcinoma that had invaded the attached gingiva of the maxilla and which on initial inspection could have been misdiagnosed as a pyogenic granuloma. With the advent of new classes of drugs to manage this disease it could be expected that this presentation may become more common.


Subject(s)
Carcinoma, Hepatocellular/secondary , Liver Neoplasms/pathology , Maxillary Neoplasms/secondary , Rare Diseases/pathology , Aged , Gingival Neoplasms/secondary , Granuloma, Pyogenic/pathology , Humans , Male
3.
Aust Dent J ; 56(2): 166-70, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21623808

ABSTRACT

BACKGROUND: Alcohol as a cofactor in interpersonal violence (IPV) has been established by studies from a number of countries. This study aimed to determine if alcohol was a cofactor in the incidence or severity of mandible fracture. METHODS: A prospective study of mandible fracture patients presenting for oral maxillofacial review over 16 months was completed. Injury severity was assessed utilizing the Mandible Injury Severity Score (MISS). RESULTS: A total of 252 facial trauma cases presented to our tertiary referral centre, 83 with fractures of the mandible. The majority of presentations were secondary to IPV (n = 54, 65.06%), 49 (90.74%) of these cases involved alcohol. Overall, alcohol was involved in 63.85% of cases (n = 53). The relative risk of requiring surgical intervention with alcohol involvement was 2.68 (CI = 1.11-9.47). Alcohol significantly increased facial fracture severity for MISS: alcohol (n = 53) 13.07 ± 5.01, no alcohol (n = 30) 11.03 ± 4.87 (p < 0.05). IPV also increased facial fracture severity for MISS: IPV (n = 54) 13.09 ± 4.90, non-IPV (n = 29) 11.00 ± 4.81 (p < 0.05). The angle of the mandible was most commonly fractured (40.5% of cases). CONCLUSIONS: Mandible fracture patients, whose injury is a result of IPV, have more severe fractures and a higher likelihood of requiring surgery if alcohol is involved. This correlates to a higher surgical workload, economic and social burden to the community. Primary alcohol and IPV prevention strategies will play an important role in reducing mandible fracture.


Subject(s)
Alcohol Drinking/epidemiology , Mandibular Fractures/epidemiology , Violence/statistics & numerical data , Accidental Falls/statistics & numerical data , Accidents, Traffic/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Athletic Injuries/classification , Athletic Injuries/epidemiology , Australian Capital Territory/epidemiology , Child , Child, Preschool , Female , Humans , Incidence , Infant , Injury Severity Score , Male , Mandibular Fractures/classification , Mandibular Fractures/surgery , Middle Aged , Prospective Studies , Risk Assessment , Young Adult
4.
Bone Marrow Transplant ; 44(11): 739-48, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19377515

ABSTRACT

We evaluated the pharmacokinetics and efficacy of oral mycophenolate mofetil (MMF) for treatment of refractory GVHD. In a prospective study of acute GVHD, 9 of 19 patients (47%) had a response and 10 (53%) had no improvement. Survival at 6 and 12 months after the start of MMF was 37 and 16%, respectively. In a retrospective study of acute GVHD, 14 of 29 patients (48%) had a response and 15 (52%) had no improvement. Survival at 6 and 12 months was 55 and 52%, respectively. In a prospective study of chronic GVHD, the cumulative incidence of disease resolution and withdrawal of all systemic immunosuppressive treatment was 9, 17 and 26% at 12, 24 and 36 months, respectively, after starting MMF. Thirteen patients (59%) required additional systemic immunosuppressive treatment for chronic GVHD. Nine of the 42 patients (21%) in the prospective studies discontinued MMF treatment because of toxicity. The area under the curve plasma concentrations of mycophenolic acid seemed to be suboptimal among patients with acute GVHD but not among those with chronic GVHD. MMF can be used effectively for treatment of GVHD.


Subject(s)
Graft vs Host Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Administration, Oral , Adolescent , Adult , Child , Child, Preschool , Female , Graft vs Host Disease/blood , Graft vs Host Disease/metabolism , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Male , Middle Aged , Mycophenolic Acid/blood , Mycophenolic Acid/pharmacokinetics , Mycophenolic Acid/therapeutic use , Prospective Studies , Retrospective Studies , Treatment Outcome , Young Adult
5.
Clin Pharmacol Ther ; 85(6): 615-22, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19295506

ABSTRACT

This study investigates the efficacy and safety of personalized cyclophosphamide (CY) dosing in 50 patients receiving CY along with total body irradiation (TBI). Participants received CY 45 mg/kg with subsequent therapeutic drug monitoring using Bayesian parameter estimation to personalize the second CY dose to a target area under the curve (AUC) for carboxyethylphosphoramide mustard (CEPM) (a reporter molecule for CY-derived toxins) and for hydroxycyclophosphamide (to ensure engraftment). The mean second CY dose was 66 mg/kg; the total dose ranged from 45 to 145 mg/kg. After completion of this phase II study, we compared participants' clinical outcomes with those of concurrent controls (n = 100) who received TBI along with standard CY doses of 120 mg/kg. Patients receiving personalized CY dosing had significantly lower postconditioning peak total serum bilirubin (P = 0.03); a 38% reduction in the hazard of acute kidney injury (AKI) (P = 0.03); and nonrelapse and overall survival rates similar to those in the controls (P = 0.70 and 0.63, respectively) despite the lower doses of CY administered to most of the patients in the personalized dosage group.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Cyclophosphamide/administration & dosage , Hematologic Neoplasms/drug therapy , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Acute Disease , Adolescent , Adult , Age Factors , Antineoplastic Agents, Alkylating/pharmacokinetics , Antineoplastic Agents, Alkylating/therapeutic use , Bayes Theorem , Bilirubin/blood , Chemical and Drug Induced Liver Injury/etiology , Combined Modality Therapy , Cyclophosphamide/pharmacokinetics , Cyclophosphamide/therapeutic use , Dose-Response Relationship, Drug , Female , Hematologic Neoplasms/mortality , Hematologic Neoplasms/radiotherapy , Humans , Kidney Diseases/chemically induced , Male , Middle Aged , Recurrence , Whole-Body Irradiation , Young Adult
6.
Bone Marrow Transplant ; 33(3): 337-46, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14647254

ABSTRACT

Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day -1 and 50 and whether the levels can be further improved by donor vaccination on day -20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50 and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365 (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D(-20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the lowest in the D(N)R(365) patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days -1 and 50 improves antibody levels and that donor vaccination on day -20 further improves the levels. In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Tissue Donors , Vaccination/methods , Adolescent , Adult , Aged , Antibodies/blood , Antibody Formation , Antigens, Bacterial/administration & dosage , Antigens, Bacterial/immunology , Bacterial Capsules/administration & dosage , Bacterial Capsules/immunology , Drug Administration Schedule , Female , Haemophilus influenzae/immunology , Hepatitis B Surface Antigens/administration & dosage , Hepatitis B Surface Antigens/immunology , Humans , Male , Middle Aged , Streptococcus pneumoniae/immunology , Tetanus Toxoid/administration & dosage , Tetanus Toxoid/immunology , Time Factors , Transplantation, Homologous , Vaccination/adverse effects
7.
Biol Blood Marrow Transplant ; 9(11): 689-97, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14652852

ABSTRACT

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a somatic mutation of the X-linked phosphatidylinositol glycan class A gene. Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning is the only curative treatment; however, it is associated with high treatment-related mortality. Here, we report on allogeneic HCT for PNH after minimal conditioning. Seven adult patients with high-risk PNH underwent peripheral blood HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m(2)/d on days -4 to -2 and 2 Gy of total body irradiation on day 0. After HCT, patients were given immunosuppressive therapy with oral cyclosporine starting on day -3 and mycophenolate mofetil starting on day 0. All 7 patients attained durable engraftment. After 28 days, a median of 77% (range, 53%-96%) T-cell donor chimerism was found in bone marrow and peripheral blood. T-cell chimerism increased to 91% (range, 76%-100%) on day +180 and to 100% in all surviving patients after 12 months. All 7 patients attained complete remissions of their disease. Four patients are alive 13 to 38 months after HCT. Three patients died of treatment-related mortality, 1 because of complications after acute pancreatitis and multiorgan failure, 1 because of infection related to chronic graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH.


Subject(s)
Hemoglobinuria, Paroxysmal/therapy , Stem Cell Transplantation/statistics & numerical data , Tissue Donors/statistics & numerical data , Transplantation Conditioning/methods , Adolescent , Adult , Anemia, Aplastic/etiology , Anemia, Aplastic/therapy , Chromosomes, Human, X , Family , Hemoglobinuria, Paroxysmal/genetics , Hemolysis , Humans , Living Donors , Middle Aged , Mutation , Treatment Outcome
8.
Bone Marrow Transplant ; 32(5): 515-22, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12942099

ABSTRACT

The incidence, etiology, outcome, and risk factors for developing pneumonia late after hematopoietic stem cell transplantation (SCT) were investigated in 1359 patients transplanted in Seattle. A total of 341 patients (25% of the cohort) developed at least one pneumonic episode. No microbial or tissue diagnosis (ie clinical pneumonia) was established in 197 patients (58% of first pneumonia cases). Among the remaining 144 patients, established etiologies included 33 viral (10%), 31 bacterial (9%), 25 idiopathic pneumonia syndrome (IPS, 7%), 20 multiple organisms (6%), 19 fungal (6%), and 16 Pneumocystis carinii pneumonia (PCP) (5%). The overall cumulative incidence of first pneumonia at 4 years after discharge home was 31%. The cumulative incidences of pneumonia according to donor type at 1 and 4 years after discharge home were 13 and 18% (autologous/syngeneic), 22 and 34% (HLA-matched related), and 26 and 39% (mismatched related/unrelated), respectively. Multivariate analysis of factors associated with development of late pneumonia after allografting were increasing patient age (RR 0.5 for <20 years, 1.2 for >40 years, P=0.009), donor HLA-mismatch (RR 1.6 for unrelated/mismatched related, P=0.01), and chronic graft-versus-host disease (GVHD; RR 1.5, P=0.007). Our data suggest that extension of PCP prophylaxis may be beneficial in high-risk autograft recipients. Further study of long-term anti-infective prophylaxis based on patient risk factors after SCT appear warranted.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Pneumonia/etiology , Adult , Female , Follow-Up Studies , Hematologic Diseases/complications , Hematologic Diseases/mortality , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation/mortality , Histocompatibility , Humans , Incidence , Infection Control , Male , Middle Aged , Pneumocystis Infections/etiology , Pneumonia/epidemiology , Pneumonia/mortality , Risk Factors , Survival Analysis , Time Factors , Treatment Outcome
9.
Blood ; 98(13): 3868-70, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11739201

ABSTRACT

This study compared the incidence of clinical extensive chronic graft-versus-host disease (GVHD), transplantation-related mortality, survival, and relapse-free survival among recipients randomly assigned to receive a 24-month or a 6-month course of cyclosporine prophylaxis after transplantation of allogeneic marrow from an HLA-identical sibling or alternative donor. Patients who did not have clinical manifestations of chronic GVHD on day 80 after transplantation were eligible for the study if they previously had acute GVHD or if a skin biopsy showed histologic evidence of chronic GVHD. Clinical extensive chronic GVHD developed in 35 of the 89 patients (39%) in the 24-month group and 37 of the 73 patients (51%) in the 6-month group. The hazard of developing chronic GVHD was not significantly different in the 2 groups (hazard ratio = 0.76; 95% confidence interval, 0.48-1.21; P =.25). In addition, there were no significant differences between the 2 groups in transplantation-related mortality, survival, or disease-free survival.


Subject(s)
Bone Marrow Transplantation , Cyclosporine/administration & dosage , Graft vs Host Disease/prevention & control , Adult , Biopsy , Bone Marrow Transplantation/mortality , Chronic Disease , Disease-Free Survival , Female , Graft vs Host Disease/pathology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Humans , Male , Prospective Studies , Risk Factors , Skin/pathology , Survival Rate , Time Factors , Transplantation, Homologous
10.
Blood ; 97(11): 3380-9, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11369627

ABSTRACT

Allogeneic peripheral blood stem cell grafts contain about 10 times more T and B cells than marrow grafts. Because these cells may survive in transplant recipients for a long time, recipients of blood stem cells may be less immunocompromised than recipients of marrow. Immune reconstitution was studied in 115 patients randomly assigned to receive either allogeneic marrow or filgrastim-mobilized blood stem cell transplantation. Between day 30 and 365 after transplantation, counts of most lymphocyte subsets were higher in the blood stem cell recipients. The difference was most striking for CD4 T cells (about 4-fold higher counts for CD45RA(high) CD4 T cells and about 2-fold higher counts for CD45RA(low/-)CD4 T cells; P <.05). On assessment using phytohemagglutinin and herpesvirus antigen-stimulated proliferation, T cells in the 2 groups of patients appeared equally functional. Median serum IgG levels were similar in the 2 groups. The rate of definite infections after engraftment was 1.7-fold higher in marrow recipients (P =.001). The rate of severe (inpatient treatment required) definite infections after engraftment was 2.4-fold higher in marrow recipients (P =.002). The difference in the rates of definite infections was greatest for fungal infections, intermediate for bacterial infections, and lowest for viral infections. Death associated with a fungal or bacterial infection occurred between day 30 and day 365 after transplantation in 9 marrow recipients and no blood stem cell recipients (P =.008). In conclusion, blood stem cell recipients have higher lymphocyte-subset counts and this appears to result in fewer infections. (Blood. 2001;97:3380-3389)


Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Immunity , Adult , B-Lymphocytes/immunology , CD4 Lymphocyte Count , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/pharmacology , Herpesvirus 3, Human/immunology , Humans , Immunoglobulin G/blood , Infections/epidemiology , Infections/immunology , Leukocyte Common Antigens/analysis , Leukocyte Count , Lymphocyte Activation , Lymphocyte Count , Lymphocyte Subsets , Male , Middle Aged , Neutrophils , Phytohemagglutinins/pharmacology , Recombinant Proteins , Simplexvirus/immunology , T-Lymphocytes/immunology
11.
J Clin Oncol ; 19(8): 2134-41, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11304765

ABSTRACT

PURPOSE: This report describes results of related or unrelated hematopoietic stem-cell transplants in 111 patients with treatment-related leukemia or myelodysplasia performed consecutively at the Fred Hutchinson Cancer Research Center between December 1971 and June 1998, and identifies patient and treatment characteristics associated with survival and relapse. PATIENTS AND METHODS: At transplantation, 56 patients had treatment-related secondary acute myeloid leukemia (AML), 15 had refractory anemia with excess blasts in transition (RAEB-T), 23 had refractory anemia with excess blasts (RAEB), 15 had refractory anemia (RA), and two had refractory anemia with ringed sideroblasts (RARS). Conditioning regimens were total-body irradiation (TBI) and chemotherapy for 60 patients, busulfan (BU) 14 to 16 mg/kg and cyclophosphamide (CY) 120 mg/kg (BUCY) for 27 patients, BU targeted to 600 to 900 ng/mL plasma steady-state concentration with 120 mg/kg CY (BUCY-t) for 22 patients, and miscellaneous chemotherapy for two patients. The donors were HLA-identical or partially identical family members for 69 patients and unrelated donors for 42 patients. RESULTS: The 5-year disease-free survival was 8% for TBI, 19% for BUCY, and 30% for BUCY-t (P =.006). The 5-year cumulative incidence of relapse was 40% for secondary AML, 40% for RAEB-T, 26% for RAEB, and 0% for RA or RARS (P =.0009). The 5-year cumulative incidence of nonrelapse mortality after TBI was 58%; after BUCY, 52%; and after BUCY-t, 42% (P =.02). CONCLUSION: Patients at risk for treatment-related leukemia or myelodysplasia should be followed closely and be considered for stem-cell transplantation early in the course of myelodysplasia using conditioning regimens such as BUCY-t designed to reduce nonrelapse mortality.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Neoplasms, Second Primary/therapy , Adult , Busulfan/administration & dosage , Cyclophosphamide/administration & dosage , Disease-Free Survival , Follow-Up Studies , Hematopoietic Stem Cell Mobilization , Humans , Leukemia, Myeloid, Acute/etiology , Mortality , Myelodysplastic Syndromes/etiology , Neoplasms, Second Primary/etiology , Prognosis , Retrospective Studies , Transplantation, Autologous , Transplantation, Homologous , Whole-Body Irradiation
12.
Transplantation ; 72(12): 1924-9, 2001 Dec 27.
Article in English | MEDLINE | ID: mdl-11773890

ABSTRACT

BACKGROUND: In a pilot trial we evaluated the toxicity and efficacy of sirolimus (rapamycin) as second-line therapy for the treatment of acute graft-versus-host disease (GVHD) in 21 patients (1-46 years of age) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: All patients were treated with methylprednisolone at 2 mg/kg/day, but failed to respond satisfactorily. Sirolimus was started 19-78 (median 37) days after HSCT when 10 patients had grade III and 11 had grade IV GVHD. The first four patients received a loading dose (15 mg/m2) of oral sirolimus on day 1 followed by 5 mg/m2/day for 13 days. The next 17 patients received either 5 (n=7) or 4 (n=10) mg/m2/day for 14 days without a loading dose. Eleven patients completed the 14-day sirolimus course. Five patients were treated for 9-13 days, two for 6 days, and three for 1-3 days. RESULTS: Sirolimus was discontinued early in 10 patients because of lack of improvement in GVHD (n=5), myelosuppression (n=2), seizure (n=2), and attending physician preference (n=1). The most common and significant adverse events were thrombocytopenia (n=7) and neutropenia (n=4). Other side effects included increased blood triglycerides (n=8) and cholesterol (n=3). Five patients had evidence of a hemolytic uremic syndrome concurrently with or after sirolimus treatment. Eighteen of the 21 patients received 6 or more doses of sirolimus and 12 responded, 5 with complete and 7 with partial responses. Six of the 12 responders (28% of all patients enrolled) and 1 nonresponder are currently alive at 400-907 days after HSCT, 3 with chronic GVHD. Fourteen of the 21 patients (66%) died 40-263 days after transplant. CONCLUSION: These data suggest that sirolimus has activity in the treatment of steroid-refractory acute GVHD. However, there was considerable toxicity and further dose optimization studies seem warranted.


Subject(s)
Glucocorticoids/therapeutic use , Graft vs Host Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Methylprednisolone/therapeutic use , Sirolimus/therapeutic use , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Drug Resistance , Female , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/pharmacokinetics , Infant , Male , Middle Aged , Pilot Projects , Retreatment , Sirolimus/adverse effects , Sirolimus/pharmacokinetics , Treatment Outcome
13.
Bone Marrow Transplant ; 26(9): 985-91, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11100278

ABSTRACT

This retrospective study describes the outcome in 53 patients who had immunosuppressive treatment changed from cyclosporine (CSP) to tacrolimus for resistant acute GVHD (n = 23), hemolytic uremic syndrome (HUS) (n = 13) or CSP-associated neurotoxicity (n = 17). Tacrolimus was administered at doses of 0.03 mg/kg/day intravenously or 0.12 mg/kg/day orally in divided doses, as tolerated. Median time of conversion to tacrolimus after transplant was day 47. Nineteen patients had treatment changed to tacrolimus for resistant acute GVHD grades III or IV, with the median day of conversion being day 49 after transplant. Two of 20 evaluable patients had a complete resolution of GVHD after changing treatment to tacrolimus, with 18 showing no improvement. Eleven evaluable patients had therapy changed to tacrolimus for CSP-associated neurotoxicity at a median of 36 days after transplant. Eight patients had resolution of neurotoxicity and three had partial improvement. Eleven evaluable patients had therapy changed to tacrolimus for HUS at a median of 46 days after transplant. One patient had complete resolution of HUS and 10 showed no response. Side-effects related to tacrolimus included renal toxicity (34%), neurotoxicity (15%) and HUS (9%). Nine (17%) patients remain alive, including six patients who had therapy changed to tacrolimus for CSP-associated neurotoxicity. While often successful for dealing with neurotoxicity, only a rare patient improved after therapy was changed from CSP to tacrolimus for HUS or resistant acute GVHD.


Subject(s)
Cyclosporine/therapeutic use , Graft vs Host Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Tacrolimus/therapeutic use , Acute Disease , Adolescent , Adult , Bone Marrow Transplantation/adverse effects , Child , Child, Preschool , Cyclosporine/adverse effects , Drug Resistance , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hemolytic-Uremic Syndrome/chemically induced , Humans , Immunosuppressive Agents/adverse effects , Kidney Diseases/chemically induced , Male , Middle Aged , Peripheral Nervous System Diseases/chemically induced , Retrospective Studies , Tacrolimus/adverse effects , Transplantation, Homologous/adverse effects , Treatment Outcome
14.
Blood ; 96(12): 3995-6, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11090092

ABSTRACT

In a randomized, placebo-controlled, double-blind trial, thalidomide or placebo together with glucocorticoids and either cyclosporine or tacrolimus was administered as initial therapy for clinical extensive chronic graft-versus-host disease (cGVHD). All patients had thrombocytopenia or cGVHD that evolved directly from acute GVHD as an indicator of a poor prognosis. The study drug (thalidomide or placebo) was administered initially at a dose of 200 mg orally per day, followed by a gradual increase to 800 mg/d if side effects were tolerable. Treatment with the study drug was discontinued before resolution of cGVHD in 23 (92%) of the 25 patients who received thalidomide and in 17 (65%) of the 26 patients who received placebo (P =.02). Neutropenia and neurologic symptoms were the most frequent reasons for early discontinuation of treatment with thalidomide. The duration of treatment with thalidomide was too short to assess its efficacy in controlling cGVHD. (Blood. 2000;96:3995-3996)


Subject(s)
Graft vs Host Disease/drug therapy , Thalidomide/administration & dosage , Actuarial Analysis , Chronic Disease , Cyclosporine/administration & dosage , Cyclosporine/toxicity , Double-Blind Method , Drug Therapy, Combination , Graft vs Host Disease/complications , Humans , Hypesthesia/chemically induced , Neutropenia/chemically induced , Prednisone/administration & dosage , Prednisone/toxicity , Thalidomide/toxicity
15.
J Clin Oncol ; 18(2): 348-57, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10637249

ABSTRACT

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3, 182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7. 5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Transplantation , Leukemia/therapy , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Second Primary/epidemiology , Whole-Body Irradiation/adverse effects , Acute Disease , Adolescent , Age Factors , Child , Child, Preschool , Cohort Studies , Female , Graft vs Host Disease/complications , Humans , Infant , Infant, Newborn , Male , Neoplasms, Radiation-Induced/etiology , Neoplasms, Second Primary/etiology , Risk Factors
16.
Haematologica ; 84(12): 1085-7, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10586209

ABSTRACT

BACKGROUND AND OBJECTIVE: Marrow transplantation results in disease-free survival for less than one-third of patients treated for secondary leukemia. The objective of this report is to review results following allogeneic marrow transplantation for treatment of secondary leukemia or myelodysplasia at a single tertiary referral center to determine the patient characteristics which lead to better survival and lower relapse. DESIGN AND METHODS: The medical records of 99 patients with secondary leukemia or myelodysplasia transplanted consecutively at the Fred Hutchinson Cancer Research Center between 1971 and 1997 were reviewed. Prior to development of secondary leukemia or myelodysplasia, the patients' original diagnoses were hematopoietic malignancies, solid tumors, aplastic anemia, or miscellaneous individual disorders previously treated by chemotherapy alone, radiation alone, chemoradiotherapy, or immunosuppressive therapy. At the time of transplantation, at each stage of myelodysplasia the numbers of patients were 52 with acute myelogenous leukemia (AML), 15 with refractory anemia with excess blasts in transition (RAEB-T), 18 with refractory anemia with excess blasts (RAEB), 11 with refractory anemia (RA), 1 with refractory anemia with ringed sideroblasts (RARS), and 2 with hypoplastic unclassifiable hematologic disorders. Sixty-five patients received marrow from an HLA identical or partially identical family member, and 34 received marrow from an HLA identical unrelated donor after conditioning with chemotherapy and total body irradiation or chemotherapy alone. RESULTS: The Kaplan-Meier probability of survival after transplantation for all patients was 13%, and by stage of disease was 33% for RA/RARS, 20% for RAEB, and 8% for RAEB-T/AML. The probability of relapse for all patients was 47%, was 34% for RAEB, and 58% for RAEB-T/AML. None of the patients with RA/RARS has relapsed. The overall probability of non-relapse mortality was 78%, divided equally among infection or organ failure-related causes of death. INTERPRETATION AND CONCLUSIONS: The main impediments to long-term survival after transplantation for secondary leukemia or myelodysplasia are relapse and mortality from infections or organ failure. The survival is better when transplantation is done during the early stages of myelodysplasia because it is then associated with a lower relapse rate. These data suggest that patients at risk of secondary myelodysplasia should be followed prospectively to detect the early stages of myelodysplasia, and be considered for transplantation at that time.


Subject(s)
Bone Marrow Transplantation , Leukemia/therapy , Myelodysplastic Syndromes/therapy , Neoplasms, Second Primary/therapy , Adolescent , Adult , Child , Child, Preschool , Follow-Up Studies , Humans , Middle Aged , Retrospective Studies , Survival Rate , Transplantation, Homologous
17.
Blood ; 94(7): 2208-16, 1999 Oct 01.
Article in English | MEDLINE | ID: mdl-10498590

ABSTRACT

We evaluated 18,014 patients who underwent allogeneic bone marrow transplantation (BMT) at 235 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders (PTLD). PTLD developed in 78 recipients, with 64 cases occurring less than 1 year after transplantation. The cumulative incidence of PTLD was 1.0% +/- 0.3% at 10 years. Incidence was highest 1 to 5 months posttransplant (120 cases/10,000 patients/yr) followed by a steep decline to less than 5/10,000/yr among >/=1-year survivors. In multivariate analyses, risk of early-onset PTLD (<1 year) was strongly associated (P <.0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymocyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for prophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P =.02) and with conditioning regimens that included radiation (RR = 2.9, P =.02). Methods of T-cell depletion that selectively targeted T cells or T plus natural killer (NK) cells were associated with markedly higher risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P =.009). The only risk factor identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P =.01). Rates of PTLD among patients with 2 or >/=3 major risk factors were 8.0% +/- 2.9% and 22% +/- 17.9%, respectively. We conclude that factors associated with altered immunity and T-cell regulatory mechanisms are predictors of both early- and late-onset PTLD.


Subject(s)
Bone Marrow Transplantation/adverse effects , Lymphoproliferative Disorders/epidemiology , Postoperative Complications/epidemiology , Adolescent , Adult , Anemia, Aplastic/therapy , Bone Marrow Transplantation/immunology , Child , Cohort Studies , Female , Graft vs Host Disease/prevention & control , Histocompatibility Testing , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Leukemia/therapy , Lymphocyte Depletion , Male , Risk Factors , T-Lymphocytes/immunology , Transplantation, Homologous , United States/epidemiology
19.
Blood ; 91(10): 3637-45, 1998 May 15.
Article in English | MEDLINE | ID: mdl-9572999

ABSTRACT

We reviewed the records and reevaluated 212 patients with aplastic anemia transplanted at the Fred Hutchinson Cancer Research Center (FHCRC) between 1970 and 1993 who survived >/=2 years and who have been followed for up to 26 years. Parameters analyzed included hematopoietic function, chronic graft-versus-host disease (GVHD), skin disease, cataracts, lung disease, skeletal problems, posttransplant malignancy, depression, pregnancy/fatherhood, and the return to work or school, as well as patient self-assessment of physical and psychosocial health, social interactions, memory and concentration, and overall severity of symptoms. Survival probabilities at 20 years were 89% for patients without (n = 125) and 69% for patients with chronic GVHD (n = 86) (the status was uncertain in 1 surviving patient). All patients had normal hematopoietic parameters. Skin problems occurred in 14%, cataracts in 12%, lung disease in 24%, and bone and joint problems in 18% of patients. Eleven patients (12%) developed a solid tumor malignancy and 19% of patients experienced depression. Chronic GVHD was the dominant risk factor for late complications. Seventeen patients died at 2.5 to 20.4 years posttransplant; 13 of these had chronic GVHD and related complications. At 2 years, 83% of patients had returned to school or work; the proportion increased to 90% by 20 years. At least half of the patients preserved or regained the ability to become pregnant or father children. Patients rated their quality of life as excellent and symptoms as minimal or mild. In conclusion, marrow transplantation in patients with aplastic anemia established long-term normal hematopoiesis. No new hematologic disorders occurred. The major cause of morbidity and mortality was chronic GVHD. However, the majority of patients who survived beyond 2 years returned to a fully functional life.


Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation/statistics & numerical data , Anemia, Aplastic/mortality , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/psychology , Cataract/epidemiology , Cataract/etiology , Cohort Studies , Depression/epidemiology , Depression/etiology , Female , Fertility , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Hematopoiesis , Humans , Lung Diseases/epidemiology , Lung Diseases/etiology , Male , Musculoskeletal Diseases/epidemiology , Musculoskeletal Diseases/etiology , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/etiology , Pregnancy , Quality of Life , Retrospective Studies , Risk Factors , Skin Diseases/epidemiology , Skin Diseases/etiology , Survival Analysis , Survival Rate , Transplantation, Homologous/adverse effects , Transplantation, Homologous/statistics & numerical data , Treatment Outcome
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