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Metastatic Merkel cell carcinoma in the bone marrow of a patient with plasma cell myeloma and therapy-related myelodysplastic syndrome.
Kressin MK, Kim AS
(2012) Int J Clin Exp Pathol 5: 1007-12
MeSH Terms: Adult, Aged, Antineoplastic Agents, Biomarkers, Tumor, Biopsy, Bone Marrow Examination, Bone Marrow Neoplasms, Carcinoma, Merkel Cell, Fatal Outcome, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Karyotyping, Male, Middle Aged, Multiple Myeloma, Myelodysplastic Syndromes, Neoplasms, Second Primary, Peripheral Blood Stem Cell Transplantation, Skin Neoplasms
Show Abstract · Added May 28, 2014
Merkel cell carcinoma is an aggressive neoplasm of the skin that shows frequent lymph node metastases, but has only rarely been reported in the bone marrow. Herein we report a case of a 64-year-old male with a history of plasma cell myeloma and recent skin diagnosis of Merkel cell carcinoma who presented for a routine follow-up bone marrow to assess his myeloma. The biopsy showed persistent plasma cell myeloma, trilineage dysplasia, and clusters of neuroendocrine cells consistent with metastatic Merkel cell carcinoma. Discussion of this case, a review of metastatic Merkel cell carcinoma, and identification of clinical settings in which staging bone marrow biopsy may be warranted are presented.
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21 MeSH Terms
Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders.
Horan J, Wang T, Haagenson M, Spellman SR, Dehn J, Eapen M, Frangoul H, Gupta V, Hale GA, Hurley CK, Marino S, Oudshoorn M, Reddy V, Shaw P, Lee SJ, Woolfrey A
(2012) Blood 120: 2918-24
MeSH Terms: Adolescent, Adult, Blood Donors, Bone Marrow Transplantation, Child, Child, Preschool, Female, Graft Rejection, Graft vs Host Disease, HLA Antigens, Hematologic Diseases, Histocompatibility, Humans, Infant, Infant, Newborn, Middle Aged, Peripheral Blood Stem Cell Transplantation, Survival Rate, Unrelated Donors, Young Adult
Show Abstract · Added March 27, 2014
The importance of human leukocyte antigen (HLA) matching in unrelated donor transplantation for nonmalignant diseases (NMD) has yet to be defined. We analyzed data from 663 unrelated marrow and peripheral blood stem cell transplants performed from 1995 to 2007 for treatment of NMD. Transplantation from a donor mismatched at the HLA-A, -B, -C, or -DRB1, but not -DQB1 or -DPB1, loci was associated with higher mortality in multivariate analyses (P = .002). The hazard ratio for mortality for single (7/8) and double mismatched (6/8) transplants was 1.29 (0.97-1.72; P = .079) and 1.82 (1.30-2.55; P = .0004), respectively, compared with 8/8 matched transplants. HLA mismatches were not associated with acute or chronic GVHD, but were strongly associated with graft failure. After adjustment for other factors, the odds ratio for graft failure for 7/8 and 6/8 (allele and/or antigen) matched pairs compared with 8/8 matched transplants was 2.81 (1.74-4.54; P < .0001) and 2.22 (1.26-3.97; P = .006), respectively. Patients with NMD should receive transplants from allele matched (8/8) donors if possible. Unlike the case with malignancies, HLA mismatching in NMD is associated with graft failure rather than GVHD.
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20 MeSH Terms
Consolidative therapy with stem cell transplantation improves survival of patients with mantle cell lymphoma after any induction regimen.
Reddy N, Greer JP, Goodman S, Kassim A, Morgan DS, Chinratanalab W, Brandt S, Englehardt B, Oluwole O, Jagasia MH, Savani BN
(2012) Exp Hematol 40: 359-66
MeSH Terms: Adult, Aged, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Bortezomib, Consolidation Chemotherapy, Cyclophosphamide, Dexamethasone, Disease-Free Survival, Doxorubicin, Female, Humans, Kaplan-Meier Estimate, Lymphoma, Mantle-Cell, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation, Prednisone, Pyrazines, Remission Induction, Retrospective Studies, Rituximab, Transplantation Conditioning, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Vincristine
Show Abstract · Added March 5, 2014
Intensive induction regimen followed by high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is frequently used to improve outcomes in patients with mantle-cell lymphoma. The comparative impact of conventional vs intensive induction regimen before transplantation is unknown. Forty-eight patients with mantle-cell lymphoma receiving SCT at our institution between January 2000 and December 2010 were included in this study. At the time of initial presentation, 43 (89.5%) had stage IV disease and 18 (37.5%) received more than one chemotherapy regimen before transplantation. Forty patients underwent auto-SCT and 7 had allogeneic SCT (allo-SCT); 1 patient had an allo-SCT for relapsed disease after auto-SCT. At the time of this analysis (median follow-up of 6 years from diagnosis and 4 years from transplantation), 40 patients (88%) were alive with a 5-year disease-free survival of 74.8%. Age, disease stage, number of regimens pre-SCT, pre-SCT disease status, and type of SCT had no impact on long-term outcomes. Importantly, there were no differences among the types of induction regimen on outcomes in this cohort receiving SCT. Based on our data, we believe that future studies should focus on strategies to prevent disease relapse rather than comparing induction regimens before stem cell transplantation.
Copyright © 2012 ISEH - Society for Hematology and Stem Cells. All rights reserved.
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28 MeSH Terms
Infusion of autologous peripheral blood stem cells in an unrelated donor who developed severe aplastic anemia following stem cell donation.
Frangoul H, Navarro WH, Confer DL, Jagasia M
(2012) Bone Marrow Transplant 47: 869
MeSH Terms: Adult, Anemia, Aplastic, Humans, Living Donors, Male, Peripheral Blood Stem Cell Transplantation, Transplantation, Autologous
Added March 27, 2014
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Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia.
Chu R, Brazauskas R, Kan F, Bashey A, Bredeson C, Camitta B, Chiang KY, Frangoul H, Gale RP, Gee A, George B, Goldman FD, Gross TG, Gupta V, Hale GA, Isola L, Ispizua AU, Lazarus H, Marsh J, Russell J, Sabloff M, Waller EK, Eapen M
(2011) Biol Blood Marrow Transplant 17: 1018-24
MeSH Terms: Adolescent, Adult, Anemia, Aplastic, Bone Marrow, Bone Marrow Transplantation, Cause of Death, Child, Female, Graft vs Host Disease, Granulocyte Colony-Stimulating Factor, HLA Antigens, Hematopoietic Stem Cell Mobilization, Histocompatibility, Humans, Leukocyte Count, Living Donors, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation, Platelet Count, Postoperative Complications, Registries, Retrospective Studies, Siblings, Survival Rate, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Young Adult
Show Abstract · Added March 27, 2014
We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n = 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA.
2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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29 MeSH Terms
Autologous stem cell transplant in a patient with Down syndrome and relapsed Hodgkin lymphoma.
Eckrich MJ, Domm J, Ho R, Whitlock JA, Frangoul H
(2009) Pediatr Blood Cancer 53: 1327-8
MeSH Terms: Antineoplastic Combined Chemotherapy Protocols, Bleomycin, Carmustine, Child, Combined Modality Therapy, Cyclophosphamide, Down Syndrome, Doxorubicin, Etoposide, Granulocyte Colony-Stimulating Factor, Hodgkin Disease, Humans, Ifosfamide, Male, Mesna, Peripheral Blood Stem Cell Transplantation, Prednisone, Procarbazine, Recurrence, Remission Induction, Transplantation Conditioning, Transplantation, Autologous, Vinblastine, Vincristine, Vinorelbine
Show Abstract · Added March 5, 2014
Children with Down syndrome (DS) are at increased risk for the development of acute leukemia but they rarely develop other hematologic malignancies or solid tumors. Despite aggressive supportive care, DS patients have increased risk of treatment related morbidity and mortality compared to other children. There are few reported cases of Hodgkin disease in children with DS, and no reported cases of successful therapy for patients with relapsed disease. We report on a child with DS and relapsed Hodgkin disease who was successfully treated with high-dose chemotherapy and autologous stem cell transplant.
(c) 2009 Wiley-Liss, Inc.
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25 MeSH Terms
Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313.
Pulsipher MA, Boucher KM, Wall D, Frangoul H, Duval M, Goyal RK, Shaw PJ, Haight AE, Grimley M, Grupp SA, Kletzel M, Kadota R
(2009) Blood 114: 1429-36
MeSH Terms: Adolescent, Adult, Bone Marrow Transplantation, Child, Child, Preschool, Disease-Free Survival, Female, Hematologic Neoplasms, Humans, Infant, Male, Myeloablative Agonists, Peripheral Blood Stem Cell Transplantation, Recurrence, Survival Rate, Time Factors, Transplantation Conditioning, Transplantation, Homologous, Whole-Body Irradiation
Show Abstract · Added March 27, 2014
The role of reduced-intensity conditioning (RIC) regimens in pediatric cancer treatment is unclear. To define the efficacy of a busulfan/fludarabine/antithymocyte globulin RIC regimen in pediatric patients ineligible for myeloablative transplantation, we completed a trial at 23 institutions in the Pediatric Blood and Marrow Transplant Consortium. Forty-seven patients with hematologic malignancies were enrolled. Sustained engraftment occurred in 98%, 89%, and 90%, and full donor chimerism was achieved in 88%, 76%, and 78% of evaluable related bone marrow/peripheral blood stem cells (BM/PBSCs), unrelated BM/PBSCs, and unrelated cord blood recipients. With a median follow-up of 24 months (range, 11-53 months), 2-year event-free survival, overall survival (OS), transplantation-related mortality, and relapse were 40%, 45%, 11%, and 43%, respectively. Univariate analysis revealed an inferior outcome when patients had undergone previous total body irradiation (TBI)-containing myeloablative transplantation (2-year OS, 23% vs 63% vs 52%, previous TBI transplantation vs no TBI transplantation vs no transplantation, P = .02) and when patients not previously treated with TBI had detectable disease at the time of the RIC procedure (2-year OS, 0% vs 63%, detectable vs nondetectable disease, P = .01). Favorable outcomes can be achieved with RIC approaches in pediatric patients in remission who are ineligible for myeloablative transplantation. This study was registered at www.clinicaltrials.gov as #NCT00795132.
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19 MeSH Terms
Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia.
Hahn T, McCarthy PL, Zhang MJ, Wang D, Arora M, Frangoul H, Gale RP, Hale GA, Horan J, Isola L, Maziarz RT, van Rood JJ, Gupta V, Halter J, Reddy V, Tiberghien P, Litzow M, Anasetti C, Pavletic S, Ringdén O
(2008) J Clin Oncol 26: 5728-34
MeSH Terms: Acute Disease, Adolescent, Adult, Bone Marrow Transplantation, Canada, Europe, Female, Graft vs Host Disease, HLA Antigens, Histocompatibility Testing, Humans, Leukemia, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Acute, Living Donors, Male, Peripheral Blood Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Reproducibility of Results, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Siblings, Time Factors, Treatment Outcome, United States, Young Adult
Show Abstract · Added March 27, 2014
PURPOSE - Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved.
PATIENTS AND METHODS - Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk.
RESULTS - Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL.
CONCLUSION - This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.
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Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment.
Pearson T, Shultz LD, Miller D, King M, Laning J, Fodor W, Cuthbert A, Burzenski L, Gott B, Lyons B, Foreman O, Rossini AA, Greiner DL
(2008) Clin Exp Immunol 154: 270-84
MeSH Terms: Animals, Bone Marrow, Cord Blood Stem Cell Transplantation, Disease Models, Animal, Graft Survival, Humans, Immunophenotyping, Interleukin Receptor Common gamma Subunit, Mice, Mice, Inbred NOD, Mice, SCID, Peripheral Blood Stem Cell Transplantation, Radiation Tolerance, Spleen, Thymus Gland, Transplantation, Heterologous
Show Abstract · Added July 7, 2015
Immunodeficient hosts engrafted with human lymphohaematopoietic cells hold great promise as a preclinical bridge for understanding human haematopoiesis and immunity. We now describe a new immunodeficient radioresistant non-obese diabetic mice (NOD) stock based on targeted mutations in the recombination activating gene-1 (Rag1(null)) and interleukin (IL)-2 receptor common gamma chain (IL2rgamma(null)), and compare its ability to support lymphohaematopoietic cell engraftment with that achieved in radiosensitive NOD.CB17-Prkdc(scid) (NOD-Prkdc(scid)) IL2rgamma(null) mice. We observed that immunodeficient NOD-Rag1(null) IL2rgamma(null) mice tolerated much higher levels of irradiation conditioning than did NOD-Prkdc(scid) IL2rgamma(null) mice. High levels of human cord blood stem cell engraftment were observed in both stocks of irradiation-conditioned adult mice, leading to multi-lineage haematopoietic cell populations and a complete repertoire of human immune cells, including human T cells. Human peripheral blood mononuclear cells also engrafted at high levels in unconditioned adult mice of each stock. These data document that Rag1(null) and scid stocks of immunodeficient NOD mice harbouring the IL2rgamma(null) mutation support similar levels of human lymphohaematopoietic cell engraftment. NOD-Rag1(null) IL2rgamma(null) mice will be an important new model for human lymphohaematopoietic cell engraftment studies that require radioresistant hosts.
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16 MeSH Terms
Mobilization of Ph chromosome-negative peripheral blood stem cells in a child with chronic myeloid leukemia after imatinib-induced complete molecular remission.
Woods-Swafford W, Vnencak-Jones CL, Loken MR, Manes B, Frangoul H
(2008) Pediatr Blood Cancer 50: 639-41
MeSH Terms: Antineoplastic Agents, Benzamides, Biomarkers, Tumor, Bone Marrow Purging, Child, Filgrastim, Forecasting, Fusion Proteins, bcr-abl, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cells, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, Male, Peripheral Blood Stem Cell Transplantation, Piperazines, Protein Kinase Inhibitors, Pyrimidines, Recombinant Proteins, Remission Induction
Show Abstract · Added March 27, 2014
Chronic myelogenous leukemia (CML) is rare in the pediatric population. Allogeneic stem cell transplant remains the only curative therapy; however, identifying a fully matched donor is not always possible. Imatinib mesylate has been shown to induce hematologic and cytogenetic response in adults and children with CML. We describe a child who achieved molecular remission with imatinib mesylate. BCR-ABL negative peripheral blood stem cells (PBSC) were successfully collected after mobilization with filgrastim.
(c) 2007 Wiley-Liss, Inc.
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22 MeSH Terms