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Jeremy T Larsen,
William J Hogan,
Ivana N Micallef,
Angela Dispenzieri,
Morie A Gertz,
David J Inwards,
Han W Tun,
Vivek Roy,
Susan M Geyer,
Jacob B Allred,
Wenting Wu,
Stephen M Ansell, Michelle A Elliott,
Ayalew Tefferi,
Luis F Porrata,
Dennis A Gastineau,
Martha Q Lacy,
Mark R Litzow
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ABSTRACT: Abstract We conducted a phase I/II trial to assess the efficacy of cladribine, thiotepa, and antithymocyte globulin as a reduced intensity conditioning regimen for refractory or high-risk hematologic malignancy. The preparative regimen consisted of cladribine 5 mg/m(2)/day for 5 days, thiotepa 200 mg/m(2)/day for 3 days, and ATG 3 mg/kg/day (day -5) followed by allogeneic peripheral blood stem cell transplantation. Twelve patients were transplanted from an HLA matched family member. Two patients were treated at dose level I but both experienced grade IV dose limiting toxicities, therefore the thiotepa dose was reduced to 133 mg/m(2)/day (dose level II). Only 2 of the next 6 patients experienced dose limiting toxicities. Median age was 46 years. At dose level II, median time to neutrophil and platelet engraftment was 17 and 20 days, respectively. The incidence of acute and chronic GVHD was 40% and 30%, respectively. Day +100 non relapse mortality was 0% and at one-year was 20%. Median overall survival was 42 months and two-year OS was 70%. Median progression free survival was 11 months, and two-year PFS was 40%. We conclude that the reduced intensity conditioning regimen of cladribine, thiotepa, and ATG achieved excellent donor chimerism with acceptable toxicity.
Leukemia & lymphoma 11/2012; · 2.40 Impact Factor
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Ming Y Lim,
Aref Al-Kali,
Aneel A Ashrani,
Kebede H Begna, Michelle A Elliott,
William J Hogan,
C Christopher Hook,
Scott H Kaufmann,
Louis Letendre,
Mark R Litzow,
Mrinal S Patnaik,
Animesh Pardanani,
Ayalew Tefferi,
Alexandra P Wolanskyj,
Diane E Grill,
Rajiv K Pruthi
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ABSTRACT: Abstract Central venous access devices (CVAD) are used for intravenous therapy in patients with hematological malignancies. There are limited data comparing catheter outcomes in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. A retrospective review comparing the incidence of early- and late CVAD-associated complications and their effect on CVAD removal was performed in AML patients undergoing induction chemotherapy between 2007 and 2011. Overall, 64 Hickman® catheters and 84 peripherally inserted central catheters (PICC) were inserted; there was a trend toward increasing use of PICCs. The rate of CVAD occlusion was higher in PICCs compared to Hickman® catheters (48.2% vs 3.2%), for a rate of 20.43 vs 1.25 per 1,000 CVAD-days (p=0.0001). There was no significant difference in the rates of CVAD-associated thrombosis, premature removal, blood stream infection (BSI), and CVAD-related BSI. Importantly, there was no significant difference in the rate of CVAD removal between Hickman® catheters and PICCs for the duration that the CVADs were in place. The choice of type of CVAD inserted in newly diagnosed patients with AML will depend on ease of catheter placement, cost, perception of frequency and severity of complications, and clinician preference.
Leukemia & lymphoma 10/2012; · 2.40 Impact Factor
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Michelle A Elliott,
Louis Letendre,
Ayalew Tefferi,
William J Hogan,
Christopher Hook,
Scott H Kaufmann,
Rajiv K Pruthi,
Animesh Pardanani,
Kebede H Begna,
Aneel A Ashrani,
Alexandra P Wolanskyj,
Aref Al-Kali,
Mark R Litzow
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ABSTRACT: Therapy-related acute promyelocytic leukemia (t-APL) is a well-recognized form of APL for which the underlying etiology has been well characterized. The pathogenesis of de novo (dn-APL) remains unknown; but epidemiologic studies have consistently identified increased body mass index (BMI), younger age, and ethnicity as possible risk factors. We analyzed demographics, clinical features, and treatment responses in a contemporary series of 64 patients treated with all-trans-retinoic acid and anthracycline-based therapy to assess for differences in these two etiologically distinct patient groups. Compared with patients with t-APL (n = 11), those with dn-APL (n = 53) had a greater median BMI (31.33 vs. 28.48), incidence of obesity (60.4% vs. 27.3%) (P = 0.04), and history of hyperlipidemia (45.3% vs. 18.2%) (P = 0.01). Fewer t-APL than dn-APL patients achieved complete remission at 63.6% vs. 92.5% respectively (P = 0.008). This was the result of a higher induction mortality rate of 36.4% vs. 7.5% respectively (P = 0.008). No cases of leukemic resistance were seen in either group. Overall survival (OS) was inferior in t-APL compared with dn-APL at 51% vs. 84%, respectively (P < 0.005), primarily as a result of higher induction mortality. Relapse occurred in nine patients (16.1%) overall, but no relapses occurred in the t-APL cohort. Our observations provide further support for the hypothesis that abnormalities in lipid homeostasis may in some way be of pathogenic importance in dn-APL. Therapy-related APL is sensitive to standard therapy with no cases of resistance or relapse seen. The inferior OS of the t-APL was due to induction mortality, possibly reflecting prior therapy.
European Journal Of Haematology 03/2012; 88(3):237-43. · 2.61 Impact Factor
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Angela Dispenzieri,
Gregory A Wiseman,
Martha Q Lacy,
Suzanne R Hayman,
Shaji K Kumar,
Francis Buadi,
David Dingli,
Krista M Laumann,
Jake Allred,
Susan M Geyer,
Mark R Litzow,
Dennis A Gastineau,
David J Inwards,
Ivana N Micallef,
Stephen M Ansell,
Luis Porrata, Michelle A Elliott,
Patrick B Johnston,
William J Hogan,
Morie A Gertz
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ABSTRACT: Multiple myeloma (MM) remains an incurable illness affecting nearly 20,000 individuals in the United States per year. High-dose melphalan (HDM) with autologous hematopoietic stem cell support (ASCT) is one of the mainstays of therapy for younger patients, but little advancement has been made with regards to conditioning regimens. We opted to combine (153)Samarium ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP), a radiopharmaceutical approved for the palliation of pain caused by metastatic bone lesions, with HDM and ASCT in a Phase II study. Individualized doses of (153)Sm were based on dosimetry and were calculated to deliver 40 Gy to the bone marrow. The therapeutic dose of (153)Sm-EDTMP was followed by HDM and ASCT. Forty-six patients with newly diagnosed or relapsed disease were treated. Study patients were compared to 102 patients contemporaneously treated with HDM and ASCT. Fifty-nine percent of study patients achieved a very good partial response (VGPR) or better. With a median follow-up of 7.1 years, the median overall survival and progression free survival (PFS) from study registration was 6.2 years (95% CI 4.6-7.5 years) and 1.5 years (1.1-2.2 years), respectively, which compared favorably to contemporaneously treated non-study patients. Addition of high-dose (153)Sm-EDTMP to melphalan conditioning appears to be safe, well tolerated, and worthy of further study in the context of novel agents and in the Phase III setting.
American Journal of Hematology 06/2010; 85(6):409-13. · 4.67 Impact Factor
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ABSTRACT: Granulocyte colony-stimulating factor (GCSF) is currently the most widely used cytokine for stem cell mobilization. There are few studies suggesting GCSF administration may induce activation of both coagulation and endothelial cells that could favor the developing of thrombotic events. We report a 58-year-old female with vasculitis and renal impairment. She was found to have an underlying monoclonal gammopathy of unknown significance (MGUS). The monoclonal protein was felt to play a role in her underlying renal disease and peripheral neuropathy. She was considered a candidate for peripheral blood stem cell transplantation to manage the monoclonal protein. During stem cell mobilization with GCSF, she developed worsening of anemia; thrombocytopenia and worsening of renal function. She was diagnosed with thrombotic microangiopathy (TMA) which was successfully treated with therapeutic plasma exchange and rituximab. It is possible that GCSF may have directly (activating endothelial cells) or indirectly (activation of underlying autoimmune disorder) contributed to TMA in this patient.
Journal of Clinical Apheresis 10/2009; 24(6):259-61. · 1.93 Impact Factor
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Morie A Gertz,
Stephen M Ansell,
David Dingli,
Angela Dispenzieri,
Francis K Buadi, Michelle A Elliott,
Dennis A Gastineau,
Suzanne R Hayman,
William J Hogan,
David J Inwards,
Patrick B Johnston,
Shaji Kumar,
Martha Q Lacy,
Nelson Leung,
Ivana N M Micallef,
Luis F Porrata,
Barbara A Schafer,
Robert C Wolf,
Mark R Litzow
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ABSTRACT: We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Analysis of hospitalization trends since inception of the program showed that 278 (39%) of the 716 patients treated completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization. We also assessed recent treatment-related mortality rates during a 33-month period after implementation of the program (between January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2% for patients with high-risk myeloma (refractory, relapsing or second or greater plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates.
Mayo Clinic Proceedings 11/2008; 83(10):1131-8. · 5.70 Impact Factor
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Pankaj Malhotra,
William J Hogan,
Mark R Litzow, Michelle A Elliott,
Dennis A Gastineau,
Stephen M Ansell,
Angela Dispenzieri,
Morie A Gertz,
Suzanne R Hayman,
David J Inwards,
Martha Q Lacy,
Ivana N Micallef,
Luis F Porrata,
Ayalew Tefferi
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ABSTRACT: In order to evaluate the long-term results of allogeneic stem cell transplantation (ASCT) in B-cell chronic lymphocytic leukemia (CLL), we reviewed the outcome of 12 consecutive CLL patients, who underwent ASCT at the Mayo Clinic prior to July, 2004. Median age was 44 years (range 18-55) and median time from diagnosis to transplant 58.5 months. All patients had failed prior fludarabine-based chemotherapy and all but two patients had chemo-resistant refractory disease at time of transplant. A 'myeloablative' conditioning regimen was used in 11 patients and 'reduced intensity' in one. Bone marrow was the source of hematopoietic stem cells in 10 patients and peripheral blood in two. Donors were matched sibling in nine patients, unrelated in two and partial phenotypic match father in one. Grade II-IV acute and chronic graft versus host disease was documented in five and four patients, respectively. To date, six patients (50%) have died including four early deaths from infection. Complete remission (CR) was documented in eight patients (66.7%) post-transplant; six are currently alive whereas one died at 7 months from infection while still in CR and one relapsed 7 months post-transplant and died later. One CR patient relapsed after 4.5 years but was successfully re-transplanted and remains in second CR for 6.5+ years. Another patient recently relapsed after 10.5 years of CR. Duration of ASCT-induced CR in the remaining four patients was 6.5+, 8.5+, 9+ and 10+ years. All surviving patients displayed excellent performance status without ongoing chronic graft versus host disease. We conclude that ASCT is an effective salvage therapy for fludarabine-refractory CLL but late relapses can occur.
Leukemia & lymphoma 10/2008; 49(9):1724-30. · 2.40 Impact Factor
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Angela Dispenzieri,
Martha Q Lacy,
Suzanne R Hayman,
Shaji K Kumar,
Francis Buadi,
David Dingli,
Mark R Litzow,
Dennis A Gastineau,
David J Inwards, Michelle A Elliott,
Ivana N Micallef,
Stephen M Ansell,
William J Hogan,
Luis F Porrata,
Patrick A Johnston,
Bekele Afessa,
Alan Bryce,
Robert A Kyle,
Morie A Gertz
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ABSTRACT: Polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome is a devastating syndrome, characterized by peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cells, skin changes, papilledema, volume overload, sclerotic bone lesions, thrombocytosis and high vascular endothelial growth factor (VEGF). High-dose chemotherapy with autologous peripheral blood stem cell transplantation (ASCT) ultimately yields excellent clinical responses, but there can be considerable peritransplant morbidity. We have treated 30 POEMS patients with ASCT at Mayo Clinic, Rochester. During transplant period, patients had high rates of fever, diarrhea, weight gain and rash (93%, 77%, 53% and 43%, respectively). Only 13% remained outpatient, and median time to discharge from hospital was transplant day 17 (range 0-175). Splenomegaly was the baseline factor that best predicted for a complicated peritransplant course. Depending on the definition used, approximately 50% of patients satisfied criteria for engraftment syndrome. Earlier and more aggressive use of corticosteroids may be associated with less complicated post-transplant courses. Median overall survival has not been reached; the treatment-related mortality was 3%. In addition, important clinical improvements and reductions in plasma VEGF levels can occur in the absence of significant decrease in the monoclonal protein. Unraveling the mechanisms of the syndrome both in the context of ASCT and in general are challenges for the future.
European Journal Of Haematology 06/2008; 80(5):397-406. · 2.61 Impact Factor
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ABSTRACT: In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating leukemic blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors, not only for achieving remission but also for relapse-free survival (RFS). However, in acute myeloid leukemia (AML) parameters of chemosensitivity have been restricted mainly to the rapidity of achievement of complete remission (CR) or the assessment of residual leukemic bone marrow blasts during aplasia. We hypothesized that the time to circulating peripheral blood blast clearance, as a potential surrogate for in vivo chemosensitivity, would have prognostic relevance in AML also. In a retrospective analysis of a cohort of 86 adult patients with AML receiving uniform induction and consolidation chemotherapy, we demonstrate that the time to clearance of circulating blasts during induction chemotherapy is an independent prognostic marker of RFS, superseding other known or established risk factors, including karyotype and number of inductions to achieve CR.
Blood 01/2008; 110(13):4172-4. · 9.90 Impact Factor
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Animesh D Pardanani,
Ross L Levine,
Terra Lasho,
Yana Pikman,
Ruben A Mesa,
Martha Wadleigh,
David P Steensma, Michelle A Elliott,
Alexandra P Wolanskyj,
William J Hogan,
Rebecca F McClure,
Mark R Litzow,
D Gary Gilliland,
Ayalew Tefferi
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ABSTRACT: Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia vera, 318 with essential thrombocythemia (ET), 88 with myelodysplastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients. The diagnosis of patients with mutant MPL alleles at the time of molecular testing was de novo MMM in 12 patients, ET in 4, post-ET MMM in 1, and MMM in blast crisis in 3. Six patients carried the MPLW515L and JAK2V617F alleles concurrently. We conclude that MPLW515L or MPLW515K mutations are present in patients with MMM or ET at a frequency of approximately 5% and 1%, respectively, but are not observed in patients with polycythemia vera (PV) or other myeloid disorders. Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease.
Blood 12/2006; 108(10):3472-6. · 9.90 Impact Factor
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ABSTRACT: Myeloid disorders constitute a subgroup of hematological malignancies that is separate from lymphoid disorders. The World Health Organization system for classification of tumors of the hematopoietic system divides myeloid disorders into acute myeloid leukemia and chronic myeloid disorders based on the presence or absence, respectively, of acute myeloid leukemia--defining morphological and cytogenetic features including the presence of 20% or more myeloblasts in either the bone marrow or the peripheral blood. A recently proposed semimolecular classification system for chronic myeloid disorders recognizes 3 broad categories: the myelodysplastic syndrome, classic myeloproliferative disorders (MPD), and atypical MPD. Classic MPD includes polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, and chronic myeloid leukemia. Both myelodysplastic syndrome and BCR/ABL-negative classic MPD were previously discussed as part of the current ongoing symposium on hematological malignancies. The current review focuses on the diagnosis and treatment of both molecularly defined and clinicopathologically assigned categories of atypical MPD: chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, chronic neutrophilic leukemia, chronic basophilic leukemia, chronic eosinophilic leukemia, idiopathic eosinophilia including hypereosinophilic syndrome, systemic mastocytosis, unclassified MPD, and eosinophilic/mast cell disorders associated with mutations of platelet-derived growth factor receptors alpha (PDGFRA) and beta (PDGFRB), FGFR1, and KIT.
Mayo Clinic Proceedings 05/2006; 81(4):553-63. · 5.70 Impact Factor
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ABSTRACT: Patients who have myelofibrosis with myeloid metaplasia (MMM) display recurrent, albeit nonspecific cytogenetic abnormalities that are diverse prognostically. For the current study, the authors explored the relation between specific cytogenetic clones and JAK2(V617F) mutational status in patients with MMM and the effects on treatment response to erythropoietin (Epo).
Concomitantly collected blood granulocytes and bone marrow were processed for JAK2(V617F) mutation analysis and cytogenetic studies, respectively. Genomic DNA was amplified by polymerase chain reaction, and fluorescent dye chemistry sequencing was performed by using the same primers that were used for amplification.
Among 105 study patients, cytogenetic abnormalities were detected in 47 patients (45%), and the JAK2(V617F) mutation was detected in 52 patients (50%). Comparison of mutational frequencies between favorable (normal, sole 13q-, or 20q- clones; n = 70 patients) and unfavorable (all other abnormalities; n = 35 patients) cytogenetic categories revealed a significantly different incidence of homozygous JAK2(V617F) between them (9% vs. 23%, respectively; P = .04). Furthermore, the mutant allele coexisted with several recurrent cytogenetic lesions. Among 25 patients who received Epo either alone (n = 17 patients) or in combination with hydroxyurea (n = 8 patients), 4 patients (16%) achieved a response, and none of them were homozygous for JAK2(V617F). Conversely, a response was more likely (P = .0001) in the presence of favorable cytogenetic abnormalities (i.e., 3 of 4 responders carried sole 13q- or 20q- clones).
Unfavorable and favorable cytogenetic clones in MMM clustered with homozygosity for JAK2(V617F) and treatment response to Epo-based therapy, respectively.
Cancer 05/2006; 106(8):1739-43. · 4.77 Impact Factor
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Angela Dispenzieri,
Martha Q Lacy,
Jerry A Katzmann,
S Vincent Rajkumar,
Roshini S Abraham,
Suzanne R Hayman,
Shaji K Kumar,
Raynell Clark,
Robert A Kyle,
Mark R Litzow, [......],
Ivana M Micallef,
Luis F Porrata, Michelle A Elliott,
Patrick B Johnston,
Philip R Greipp,
Thomas E Witzig,
Steven R Zeldenrust,
Stephen J Russell,
Dennis Gastineau,
Morie A Gertz
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ABSTRACT: The immunoglobulin free light chain (FLC) is the precursor protein of amyloid in primary systemic amyloidosis (AL). Historically, the ability to monitor the amyloid protein precursor protein has been crude. We evaluated the utility of the FLC assay in a retrospective analysis of patients with AL undergoing peripheral blood stem cell transplantation (PBSCT). Ninety-three such patients had serial FLC measurements performed. The prognostic effects of the initial concentration and the extent of reduction of monoclonal FLC on survival were studied. There was a significantly higher risk of death in patients with higher baseline FLC (hazard ratio 2.6, P < .04). Baseline FLC correlated with serum cardiac troponin levels, and higher FLC levels were associated with more organs involved by amyloid, suggesting that high FLC levels may be associated with more advanced disease. The percent FLC reduction did not predict for survival, but the absolute level of FLC achieved after therapy did. Normalization of FLC level after PBSCT predicted for both organ response and complete hematologic response. Achievement of FLC response was a better predictor of survival than achievement of complete hematologic response or normalization of the FLC ratio. FLC measurements both before and after PBSCT are important predictors of patient outcome.
Blood 04/2006; 107(8):3378-83. · 9.90 Impact Factor
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Michelle A Elliott
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ABSTRACT: The World Health Organization (WHO) classification of myeloid disorders has provided updated parameters for the consistent diagnosis of two previously less than optimally defined chronic myeloid disorders, CNL and CMML. The classification of these disorders, which had been controversial, is now better defined and provides more clinically and biologically relevant disease definitions to enable uniform diagnosis and a framework to evaluate natural history and therapeutic interventions. CNL is now recognized as a distinct entity among the chronic myeloproliferative disorders and CMML is included within the new category of 'myelodysplastic/myeloproliferative diseases' (MDS/MPD). Predominant neutrophilia defines CNL whereas CMML is defined by predominant and monocytosis. In each case these defining features must be distinguished from reactive causes for the same in the absence of clear evidence of myeloid clonality (CNL and CMML) or dysplasia (CMML). The exclusion of underlying bcr/abl-driven oncogenesis is an essential component in the diagnosis of these chronic leukemic processes. The optimal therapy for both CNL and CMML remains uncertain. Current management decisions are based on small studies or extrapolated from therapeutic strategies that are effective in similar chronic, clonal myeloid disorders. Given the potential for evolution to acute leukemia or progressive refractory leucocytosis or cytopenias, allogeneic stem cell transplantation might be appropriate for younger patients. Continued reporting and investigation of specific therapeutic strategies and responses must be encouraged.
Bailliè re s Best Practice and Research in Clinical Haematology 02/2006; 19(3):571-93. · 2.64 Impact Factor
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ABSTRACT: We describe a patient with a suspected myelodysplastic syndrome that developed in association with a neurologic disorder resembling subacute combined degeneration but without vitamin B12 deficiency. Ultimately, the hematologic manifestations and the neurologic syndrome were linked to severe copper deficiency. Prompt and complete reversal of the hematologic abnormalities occurred with copper replacement. Serum copper determination should be included in the work-up of patients with anemia and leukopenia of unclear etiology who have associated myeloneuropathy. The hematologic picture can resemble sideroblastic anemia or myelodysplastic syndrome. Hyperzincemia can be an accompanying abnormality even without exogenous zinc ingestion. The reason for the copper deficiency may not be evident.
Mayo Clinic Proceedings 08/2005; 80(7):943-6. · 5.70 Impact Factor
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ABSTRACT: The current study of 153 subjects with both classic and atypical myeloproliferative disorders suggests that neutrophil polycythemia rubra vera-1 (PRV-1) over-expression is a non-specific feature of clonal myeloproliferation that displays significant correlation with leukocyte alkaline phosphatase score. These observations undermine the utility of the PRV-1 assay as a diagnostic test of additional value.
Haematologica 04/2005; 90(3):406-8. · 6.42 Impact Factor
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ABSTRACT: Patients with essential thrombocythemia (ET) and polycythemia vera (PV) have a paradoxical predisposition to bleeding and thrombotic complications that are major causes of morbidity and mortality. Bleeding manifestations are often associated with extreme thrombocytosis that may lead to acquired von Willebrand syndrome (AVWS). Symptomatic AVWS, in this instance, is managed by platelet cytoreductive therapy and, in case of a life-threatening situation, platelet apheresis may be of additional value. Qualitative platelet defects are prevalent in PV and ET but have not been consistently linked to clinical bleeding. However, in vitro and in vivo hemostatic defects in these disorders are either precipitated or exacerbated by the use of aspirin or other nonsteroidal anti-inflammatory drugs. Additional patient management issues are raised during systemic anticoagulation and surgery. This review summarizes putative pathogenetic mechanisms of bleeding and their management in ET and PV.
Current hematology reports 10/2004; 3(5):344-51.
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Angela Dispenzieri,
Morie A Gertz,
Robert A Kyle,
Martha Q Lacy,
Mary F Burritt,
Terry M Therneau,
Joseph P McConnell,
Mark R Litzow,
Dennis A Gastineau,
Ayalew Tefferi, [......],
S Vincent Rajkumar,
Rafael Fonseca,
Philip R Greipp,
Thomas E Witzig,
John A Lust,
Steven R Zeldenrust,
Denise S Snow,
Susan R Hayman,
Christopher G A McGregor,
Allan S Jaffe
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ABSTRACT: Primary systemic amyloidosis (AL) is a fatal plasma cell disorder. Pilot data suggest survival is better in patients undergoing peripheral blood stem cell transplantation (PBSCT), but the selection process makes the apparent benefit suspect. We have reported that circulating cardiac biomarkers are the best predictors of survival outside of the transplantation setting. We now test whether cardiac troponins (cTnT and cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are prognostic in transplant recipients. In 98 patients with AL undergoing PBSCT, serum cardiac biomarkers were measured (cTnT, 98 patients; cTnI, 65 patients; and NT-proBNP, 63 patients). Elevated levels of cTnT, cTnI, and NT-proBNP were present in 14%, 43%, and 48% of patients, respectively. At 20 months median follow-up, median survival has not been reached for patients with values below the thresholds; in patients with values above the thresholds, median survival is 26.1 months, 66.1 months, and 66.1 months, respectively. Our previously reported risk systems incorporating these markers were also prognostic, notably the cTnT/NT-proBNP staging. Using this system, 49%, 38%, and 13% of patients were in stage I, stage II, and stage III, respectively. Determining levels of circulating biomarkers may be the most powerful tool for staging patients with AL undergoing PBSCT.
Blood 10/2004; 104(6):1881-7. · 9.90 Impact Factor
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ABSTRACT: Thromboembolism (TE) is a known complication of L-asparaginase (ASP) therapy of acute lymphoblastic leukemia (ALL), possibly attributable to reduced synthesis of natural anticoagulants, in particular antithrombin (AT). This retrospective single institution study was performed to determine the TE incidence among adults undergoing induction with contemporary, ASP-containing regimens. Ten of 54 (18.5%) consecutive adults developed symptomatic, objectively confirmed TE, at a median of 5.5 days after the first ASP dose. These were notable for CNS and upper extremity localization, varied significantly according to ALL immunophenotype (precursor B: 11% vs. T cell: 33%), without apparent effect of schedule or total dose of ASP. Median baseline AT level was 94% and fell to a nadir of 47% (P < 0.0001) during ASP therapy. Prophylactic AT had been given to 17 during ASP therapy. None of these developed TE vs. 10/37 (27%) without replacement (P = 0.021). These observations merit further study to gain insight into disease and/or therapy-specific pathogenesis of TE in this population and call for the prospective evaluation of appropriate prophylactic interventions.
Leukemia and Lymphoma 08/2004; 45(8):1545-9. · 2.58 Impact Factor
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ABSTRACT: To present the results of a long-term analysis of 2 sequential phase 2 trials of thalidomide (alone or in combination) for palliation of myelofibrosis with myeloid metaplasia (MMM).
We analyzed (March 1999 to August 2003) initial and long-term outcomes from 36 patients with symptomatic MMM who had enrolled in either our thalidomide single-agent trial (n=15) or our trial of low-dose thalidomide (50 mg/d) combined with prednisone (n=21).
Among the 36 study patients, 20 (56%) showed some improvement in their clinical course. Response rates for specific end points included improvements in anemia (15 of 36 [42%]), thrombocytopenia (10 of 13 [77%]), or splenomegaly (5 of 30 [17%]). The combination of low-dose thalidomide and prednisone, as opposed to single-agent thalidomide, was better tolerated and more efficacious. After a median follow-up of 25 months (range, 20-56 months), 10 of 36 patients (28%) showed an ongoing response, including 8 patients in whom protocol treatment has been discontinued for a median of 21 months (range, 16-31 months). Durable treatment responses were documented for only anemia and thrombocytopenia. Treatment response was not affected by the baseline status of bone marrow fibrosis, angiogenesis, osteosclerosis, cytogenetics, or circulating myeloid progenitor (CD34) cell count. Unusual drug effects, all reversible, included leukocytosis (8 patients) and/or thrombocytosis (6 patients).
Thalidomide (alone or combined with prednisone) is an effective first-line treatment of symptomatic anemia or thrombocytopenia in MMM. Thalidomide-based therapy has the potential to produce durable responses in MMM-associated cytopenias, even after discontinuation of the drug.
Mayo Clinic Proceedings 08/2004; 79(7):883-9. · 5.70 Impact Factor
