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International Journal of Radiation... May 2011Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML)...
Impact of cranial irradiation added to intrathecal conditioning in hematopoietic cell transplantation in adult acute myeloid leukemia with central nervous system involvement.
PURPOSE
Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC).
METHODS AND MATERIALS
From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT).
RESULTS
The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality.
CONCLUSIONS
CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Central Nervous System Neoplasms; Combined Modality Therapy; Confidence Intervals; Cranial Irradiation; Cyclophosphamide; Disease-Free Survival; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Injections, Spinal; Leukemia, Myeloid, Acute; Male; Middle Aged; Proportional Hazards Models; Transplantation Conditioning; Vidarabine; Young Adult
PubMed: 20584584
DOI: 10.1016/j.ijrobp.2010.01.062 -
Biology of Blood and Marrow... Apr 2010Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of follicular non-Hodgkin lymphoma in adults is presented and... (Review)
Review
Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in the therapy of follicular non-Hodgkin lymphoma in adults is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations reached unanimously by a panel of follicular lymphoma experts are: (1) autologous SCT is recommended as salvage therapy based on pre-rituximab data, with a significant improvement in overall survival (OS) and progression-free (PFS) survival; (2) autologous SCT is not recommended as first-line treatment for most patients because of no significant improvement in OS; (3) autologous SCT is recommended for transformed follicular lymphoma patients; (4) reduced intensity conditioning before allogeneic SCT appears to be an acceptable alternative to myeloablative regimens; (5) an HLA-matched unrelated donor appears to be as effective an HLA-matched related donor for reduced intensity conditioning allogeneic SCT. There are insufficient data to make a recommendation on the use of autologous SCT after rituximab-based salvage therapy. Eleven areas of needed research in the treatment of follicular lymphoma with SCT were identified and are presented in the review.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Evidence-Based Medicine; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Follicular; Prognosis; Rituximab; Transplantation Conditioning
PubMed: 20114084
DOI: 10.1016/j.bbmt.2010.01.008 -
Biology of Blood and Marrow... Oct 2014We investigated the impact of patient and disease characteristics, including cytogenetics, previous therapy, and depth of response, on the outcome of allogeneic...
We investigated the impact of patient and disease characteristics, including cytogenetics, previous therapy, and depth of response, on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with myelodysplastic syndrome (MDS). We analyzed 256 MDS patients who underwent transplantation from a matched related (n = 133) or matched unrelated (n = 123) donor after 2001. Of the 256, 78 (30.5%) did not receive cytoreductive therapy before HSCT; 40 (15.6%) received chemotherapy, 122 (47.7%) received hypomethylating agents (HMA), and 16 (6.2%) received both (chemo+HMA). Disease status at HSCT defined by International Working Criteria was complete remission in 46 (18%) patients. There were significant differences between therapy groups: there were more therapy-related MDS and higher use of matched related donor in the untreated group. The chemotherapy group had higher serum ferritin levels at HSCT. Patients were older and had more high-risk disease by revised International Prognostic Scoring in the HMA group. Despite those differences, transplantation outcomes were similar in patients who were untreated and who received cytoreductive therapy before HSCT. Three-year event-free survival (EFS) was 44.2%, 30.6%, 34.2%, and 32.8% for untreated, chemotherapy, HMA, and chemo+HMA groups, respectively (P = .50). Multivariate analyses revealed that older age (hazard ratio [HR], 1.3; P = .001); high-risk histologic subtypes, including refractory anemia with excess blasts (HR, 1.5; P = .05) and chronic myelomonocytic leukemia (HR, 2.1; P = .03), high-risk cytogenetics with monosomal karyotype (MK) (HR, 4.0; P < .0001) and high serum ferritin level at HSCT (HR, 1.8; P = .002) were poor prognostic factors for EFS. Bone marrow blast count 5% or higher at HSCT (HR, 1.6; P = .01) and MK (HR, 4.2; P < .0001) were the only prognostic factors for increased relapse incidence after HSCT. Patients with MK represented a poor prognostic group, with 3-year EFS of 11.4% and relapse incidence of 60.9%. In this analysis, various therapy approaches before HSCT did not lead to different transplantation outcomes. Cytogenetics defined by MK was able to identify a very poor prognostic groups that innovative transplantation approaches to improve outcomes are urgently needed.
Topics: Age Factors; Antimetabolites, Antineoplastic; Cytogenetic Analysis; DNA Methylation; Female; Ferritins; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Male; Middle Aged; Monosomy; Myeloablative Agonists; Myelodysplastic Syndromes; Prognosis; Recurrence; Retrospective Studies; Risk Factors; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Unrelated Donors
PubMed: 24953017
DOI: 10.1016/j.bbmt.2014.06.022 -
British Journal of Clinical Pharmacology May 2010To i) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach, ii) identify clinical factors that affect melphalan disposition...
AIMS
To i) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach, ii) identify clinical factors that affect melphalan disposition and iii) evaluate the role of melphalan exposure in melphalan-related toxicity and disease response.
METHODS
Population pharmacokinetic modelling (using NONMEM) was performed with total and unbound concentration-time data from 100 patients (36-73 years) who had received a median 192 mg m(-2) melphalan dose. Model derived estimates of total and unbound melphalan exposure (AUC) in patients with serious melphalan toxicity and those who had a good disease response (>or=90% decrease in paraprotein concentrations) were compared using the Mann-Whitney test.
RESULTS
A two compartment model generated population mean estimates for total and unbound melphalan clearance (CL) of 27.8 and 128 l h(-1), respectively. Estimated creatinine clearance, fat free mass and haematocrit were important determinants of total and unbound CL, reducing the inter-individual variability in total CL from 34% to 27% and in unbound CL from 42% to 30%. Total AUC (range 4.9-24.4 mg l(-1) h) and unbound AUC (range 1.0-6.5 mg l(-1) h) were significantly higher in patients who had oral mucositis (>or=grade 3) and long hospital admissions (P < 0.01). Patients who responded well had significantly higher unbound AUC (median 3.2 vs. 2.8 mg l(-1) h, P < 0.05) when assessed from diagnosis to post-melphalan and higher total AUC (median 21.3 vs. 13.4 mg l(-1) h, P= 0.06), when assessed from pre- to post-melphalan.
CONCLUSIONS
Creatinine clearance, fat free mass and haematocrit influence total and unbound melphalan plasma clearance. Melphalan exposure is related to melphalan toxicity while the association with efficacy shows promising trends that will be studied further.
Topics: Adult; Aged; Area Under Curve; Creatine; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Melphalan; Metabolic Clearance Rate; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Paraproteins; Statistics, Nonparametric; Transferrin; Transplantation, Autologous
PubMed: 20573084
DOI: 10.1111/j.1365-2125.2010.03638.x -
Cancer Dec 2008The 5-year freedom from treatment failure (FFTF) rate, with treatment failure defined as the lack of post-treatment complete remission (CR), recurrence, or death, ranges... (Randomized Controlled Trial)
Randomized Controlled Trial
Early versus late intensification for patients with high-risk Hodgkin lymphoma-3 cycles of intensive chemotherapy plus low-dose lymph node radiation therapy versus 4 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine plus myeloablative chemotherapy with autologous stem cell...
BACKGROUND
The 5-year freedom from treatment failure (FFTF) rate, with treatment failure defined as the lack of post-treatment complete remission (CR), recurrence, or death, ranges from 60% to 70% after 6 to 8 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), which is the reference treatment for patients with advanced Hodgkin lymphoma (HL). In this randomized, phase 2 study, the authors tested 2 intensive chemotherapy regimens in 158 patients with clinical stage (CS) IIB through IV HL accompanied by high-risk factors who were recruited between May 1997 and December 2004.
METHODS
High-risk CS IIB, III, and IV were defined by the presence of > or =5 involved lymphoid areas, and/or a mediastinal mass ratio > or =0.45, and/or > or =2 extra lymph node sites affected by the disease (for CS IV). In Arm V, 82 patients received 3 courses of combined vindesine (5 mg/m(2)), doxorubicin (99 mg/m(2)), carmustine (140 mg/m(2)), etoposide (600 mg/m(2)), and methylprednisolone (600 mg/m(2)) (VABEM) followed by low-dose lymph node irradiation. In Arm A, 76 patients received 4 cycles of ABVD followed by myeloablative combined carmustine (300 mg/m(2)), etoposide (800 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)) and underwent autologous stem cell transplantation.
RESULTS
After 3 cycles of VABEM, the CR rate was 89% versus 60% after 4 cycles of ABVD. However, after the completion of treatment, the CR rates for Arms V and A were similar (89% and 88%, respectively). The 5-year FFTF rates for Arms V and A also were similar (79% and 75%, respectively) along with the 5-year overall survival rates (87% and 86%, respectively).
CONCLUSIONS
Early intensification (Arm V) and late intensification (Arm A) were equally effective for treating patients with high-risk/advanced HL.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphatic Irradiation; Male; Methylprednisolone; Prednisone; Treatment Outcome; Vinblastine; Vincristine
PubMed: 18988286
DOI: 10.1002/cncr.23979 -
Pediatric Blood & Cancer Nov 2012The Pediatric Oncology Group performed a pilot study to assess the feasibility of tandem high dose chemotherapy (HDC) with stem cell rescue (HDC/SCR). We report here the...
Feasibility of a tandem autologous peripheral blood stem cell transplant regimen for high risk neuroblastoma in a cooperative group setting: a Pediatric Oncology Group study: a report from the Children's Oncology Group.
BACKGROUND
The Pediatric Oncology Group performed a pilot study to assess the feasibility of tandem high dose chemotherapy (HDC) with stem cell rescue (HDC/SCR). We report here the results of this single arm trial of induction chemotherapy, local control measures (surgery and local radiation), and tandem HDC/SCR.
PROCEDURE
Patients with high risk neuroblastoma (NBL) underwent five cycles of induction chemotherapy and resection of primary tumors. Peripheral blood stem cells (PBSC) were collected after Course 3 without exvivo manipulation. Myeloablative chemotherapy was performed in rapid sequence after induction chemotherapy and surgery. The ability of patients to complete both cycles of HDC/SCR was a primary endpoint. Transplant-related toxicity, progression-free survival (PFS) and overall survival (OS) were recorded.
RESULTS
A total of 33 patients were enrolled. Twenty-two patients completed at least one HDC/SCR procedure and 17 patients completed both. Only one patient had insufficient stem cells collected for both transplants. There was one transplant-related death; engraftment was rapid and toxicity was as expected. The PFS of the 33 patients treated on this study is 24.2% ± 7.5% and OS is 36.4% ± 8.4% at 5 years. For patients who received at least one transplant PFS is 36.4% ± 11.0% and OS is 45.5% ± 11.2% at 5 years.
CONCLUSIONS
The treatment of high risk NBL with tandem HDC/SCR is feasible in terms of transplant-related mortality and the ability to collect adequate PBSC for two transplants. The outcomes from this intensified treatment have been used to design a Children's Oncology Group Phase III study testing the efficacy of tandem HDC/SCR.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Humans; Infant; Male; Neuroblastoma; Peripheral Blood Stem Cell Transplantation; Survival Rate; Transplantation, Autologous
PubMed: 22744917
DOI: 10.1002/pbc.24207 -
Biology of Blood and Marrow... Jul 2011We retrospectively analyzed the outcomes of all acute myelogenous leukemia (AML) patients in first remission (n = 44; median age = 48 years; high-risk cytogenetics =...
We retrospectively analyzed the outcomes of all acute myelogenous leukemia (AML) patients in first remission (n = 44; median age = 48 years; high-risk cytogenetics = 59%) who received unrelated donor hematopoietic cell transplantation (HCT) with myeloablative conditioning regimen of i.v. busulfan, fludarabine, and antithymocyte globulin (ATG) between January 2002 and November 2009 at our institution. Donor-recipient pairs were matched by high-resolution HLA-A, -B, -C, -DRB1, and -DQB1 typing (10/10 matches, n = 41; 9/10 matches, n = 3). With a median follow-up of 34 months, actuarial 3-year event-free survival (EFS) and overall survival (OS) is 70% and 78%, respectively. The 3-year EFS and OS in patients with and without poor risk cytogenetics is similar (63% versus 82%, P = 0.43 and 78% versus 82%, P = .89, respectively). The 3-year EFS and OS is also similar in patients above age 55 year versus patients age 55 year or younger (80% versus 67%, P = .47 and 80% versus 78%, P = .81, respectively). The 100-day and 3-year cumulative incidence of transplant-related mortality is 5% and 15%, respectively. Six patients have relapsed, and 3 of them are alive and in remission after salvage therapy, with a median follow-up of 23 months. These results indicate that the majority of AML patients eligible for this treatment can achieve long-term disease control.
Topics: Adolescent; Adult; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Clinical Trials as Topic; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Graft vs Host Disease; Humans; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Living Donors; Male; Middle Aged; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Remission Induction; Retrospective Studies; Salvage Therapy; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult
PubMed: 21087679
DOI: 10.1016/j.bbmt.2010.11.012 -
Biology of Blood and Marrow... Nov 2014The role of allogeneic (allo-) and autologous stem cell transplantation (auto-SCT) in the management of patients with transformed indolent nonfollicular non-Hodgkin...
The role of allogeneic (allo-) and autologous stem cell transplantation (auto-SCT) in the management of patients with transformed indolent nonfollicular non-Hodgkin lymphoma is unknown. This is a multicenter, retrospective cohort study of patients with biopsy-proven indolent B cell nonfollicular non-Hodgkin lymphoma and simultaneous or subsequent biopsy-proven aggressive histology transformation who were treated with allo-SCT or auto-SCT between 1996 and 2013. All patients received myeloablative conditioning regimens. Outcomes were compared with a cohort of 246 patients with transformed follicular lymphoma who also underwent allo-SCT (n = 47) or auto-SCT (n = 199) across the same institutions and time frame. Thirty-four patients were identified with the following underlying indolent histologies: 15 (44%) marginal zone lymphoma, 11 (32%) chronic lymphocytic leukemia, 6 (18%) small lymphocytic lymphoma, and 2 (6%) lymphoplasmacytic lymphoma. Patients received various anthracycline or platinum-containing chemotherapy regimens for transformation, incorporating rituximab in 25 (74%). Twelve (35%) subsequently underwent allo-SCT, whereas 33 (65%) underwent auto-SCT. The 3-year overall survival rate after transplantation was 67% (allo-SCT 54%, auto-SCT 74%), and 3-year progression-free survival rate was 49% (allo-SCT 40%, auto-SCT 54%). The 3-year nonrelapse mortality rate was 14% (allo-SCT 15%, auto-SCT 7%). Transplant-related mortality at 100 days was 17% for allo-SCT and 0% for auto-SCT. Adjusted for type of stem cell transplantation, 3-year overall survival, progression-free survival, and nonrelapse mortality rates were similar to those of patients with transformed follicular lymphoma receiving allo-SCT and auto-SCT (P = .38, P = .69, and P = .54, respectively). Allo-SCT and auto-SCT may be reasonable treatments for selected patients with transformed nonfollicular indolent lymphoma, although medium-term outcomes and toxicity appear to be more favorable with auto-SCT.
Topics: Adult; Aged; Anthracyclines; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Combined Modality Therapy; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Rituximab; Survival Rate; Transplantation Conditioning; Treatment Outcome
PubMed: 25042735
DOI: 10.1016/j.bbmt.2014.07.015 -
Journal of Clinical and Experimental... 2015We report a case of intraocular relapse of extranodal NK/T-cell lymphoma with anterior chamber hypopyon and retinal infiltrates. A 55-year-old man developed fever,...
We report a case of intraocular relapse of extranodal NK/T-cell lymphoma with anterior chamber hypopyon and retinal infiltrates. A 55-year-old man developed fever, malaise, anorexia, and hepatosplenomegaly, and was diagnosed with NK/T-cell lymphoma by liver biopsy. He underwent 2 courses of SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy, followed by myeloablative peripheral blood stem cell transplantation, donated by his brother. Two months later, he developed high-grade fever, hepatosplenomegaly, and peritoneal lymphadenopathy, and the relapse with hemophagocytic syndrome was diagnosed by bone marrow biopsy. He underwent 2 courses of SMILE salvage chemotherapy, followed by non-myeloablative peripheral blood stem cell transplantation, donated by his son. Two months later, he noticed blurred vision in both eyes. The right eye had aqueous cells and keratic precipitates, but no retinal lesions. The left eye had hypopyon in the anterior chamber with numerous aqueous cells, and retinal white infiltrates with retinal hemorrhages. The aqueous cells, obtained by anterior chamber paracentesis, were positive for CD3, CD56, and Epstein-Barr virus-encoded RNA, but negative for CD20 by immunocytochemical staining. Head magnetic resonance imaging demonstrated white matter lesions in the anterior to parietal lobes on the right side. The patient underwent intrathecal methotrexate injection and external beam radiation at 40 Gy, covering the entire brain and both eyes. The retinal lesions and hypopyon disappeared. Two months later, the patient died of renal failure, and autopsy demonstrated multi-organ involvement of lymphoma cells. In conclusion, we report a case of NK/T-cell lymphoma relapse with intraocular lesions, after combined chemotherapy and hematopoietic stem cell transplantation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow; Fatal Outcome; Humans; Intraocular Lymphoma; Liver; Lymphoma, Extranodal NK-T-Cell; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation
PubMed: 26763364
DOI: 10.3960/jslrt.55.157 -
Neuro-oncology Apr 2000The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent... (Comparative Study)
Comparative Study
The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Transplantation; Brain Diseases; Brain Neoplasms; Cachexia; Cerebral Hemorrhage; Cisplatin; Disease Progression; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Karnofsky Performance Status; Lomustine; Male; Middle Aged; Neoplasm Recurrence, Local; Oligodendroglioma; Procarbazine; Survival Analysis; Survival Rate; Thiotepa; Treatment Failure; Vincristine
PubMed: 11303620
DOI: 10.1093/neuonc/2.2.114