Papers by Makiko Ban-Hoefen
Journal of Vascular Surgery, Feb 1, 2010
Conclusion: Botox appears to provide improvement in digital perfusion and pain reduction in patie... more Conclusion: Botox appears to provide improvement in digital perfusion and pain reduction in patients with Raynaud's syndrome when conservative management fails. Summary: Digital ulceration associated with Raynaud's syndrome is painful, difficult to treat, and frequently results in patient debilitation and chronic depression. Reports by Sycha and Van Beek have indicated potential benefit for patients with ischemic digits with local injection of botulinum toxin (
PubMed, 2008
Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We des... more Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We describe the case of a 77-year-old man who had initially been diagnosed with a left atrial mass on an echocardiogram, presenting with progressive dyspnea, dysphagia, odynophagia and fevers. The cardiac mass had been managed as an outpatient with full anticoagulation for the suspicion of clot. On admission, cardiac magnetic resonance imaging revealed a large mediastinal mass invading the left atrium that originated from the oesophagus. A barium oesophagram revealed an apple core lesion involving the distal third of the oesophagus. A subsequent computed tomography scan demonstrated a large mediastinal soft tissue mass and paratracheal lymphadenopathy. A flexible upper endoscopy revealed an oesophageal mass that was approximately 10 cm in length, irregular at the margins, and with a very necrotic appearance. This was biopsied, revealing findings consistent with high grade diffuse large B cell lymphoma. This case illustrates lymphoma presenting with dyspnea, odynophagia and a left atrial mass. To our knowledge, there are no reported cases of diffuse large B cell lymphoma presenting as odynophagia and a cardiac mass.
Thrombosis Research, Jun 1, 2009
Heparin-induced thrombocytopenia (HIT) results from development of an antibody to a complex of he... more Heparin-induced thrombocytopenia (HIT) results from development of an antibody to a complex of heparin and platelet factor 4 (PF4) resulting in thrombocytopenia and a prothrombotic state with serious clinical consequences. The diagnosis depends on a combination of both the clinical presentation and laboratory detection of an appropriate antibody. To determine the frequency, clinical characteristics and laboratory correlates of HIT in a tertiary care hospital. A retrospective review of all case of HIT over a thirty month period in a tertiary care hospital was conducted. HIT was diagnosed in 136 patients including 114/28,091 (0.48%) of those receiving only unfractionated heparin, 22/6,559 (0.33%) of those that received both unfractionated and low-molecular-weight heparin (LMWH) and in 2/2498 (0.08%) of those receiving only LMWH (P=0.02 compared to those receiving only unfractionated heparin). HIT occurred in 62/16,939 patients (0.39%) of patients receiving subcutaneous (SC) heparin or LMWH compared to 69/11,152 (0.62%) of patients receiving intravenous (IV) therapy (P=0.003). Of all patients with exposure to heparin products, 41/34,650 (0.1%) developed symptomatic thrombosis. The optical density (OD) of the ELISA was significantly higher in patients with HIT and thrombosis (1.2 +/- 0.8) compared to those without thrombosis (0.9 +/- 0.6, P=0.03). HIT develops in approximately 0.4% of all patients exposed to heparin at a tertiary care hospital but is significantly less frequent in those treated with LMWH only than in those who receive unfractionated heparin. A higher antibody titer is associated with the development of thrombosis. The occurrence of HIT could be decreased by reducing exposure to unfractionated heparin, and the diagnosis could be improved by reporting the OD of the ELISA test result.
British Journal of Haematology, Sep 20, 2013
Histological transformation (HT) is a major cause of morbidity and mortality in patients with ind... more Histological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were identified. Treatments for HT included autologous stem-cell transplant (auto-SCT) (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto-SCT patients aged ≤60 years (n = 24), the 2-year OS was 74%. For nontransplanted patients aged ≤60 years (n = 19), the 2-year OS was 59%. The 2-year OS of patients na€ ıve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0Á03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era.
Blood, Nov 16, 2012
Abstract 2669 Background The prognosis of histologic transformation (HT) of indolent…
Journal of investigative medicine high impact case reports, Jul 1, 2016
Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the ... more Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies.
The New England Journal of Medicine, Aug 4, 2016
Chuvash polycythemia is a rare congenital polycythemia caused by a homozygous R200W (c.598C→T) ge... more Chuvash polycythemia is a rare congenital polycythemia caused by a homozygous R200W (c.598C→T) germline mutation in the von Hippel-Lindau gene (VHL). 1,2 Patients with Chuvash polycythemia present with erythrocytosis and symptoms such as headache, dizziness, dyspnea, and plethora. 1,3 The disease is associated with an increased risk of hemorrhage, thrombosis, and early death. 1,3,4 Intermittent phlebotomy has been used in the management of Chuvash polycythemia without clearly established efficacy. 3,4 The VHL protein has been shown to target phosphorylated Janus kinase 2 (pJAK2) for ubiquitinmediated degradation. 5 Treatment of Vhl R200W/R200W-knock-in mice with a JAK2 inhibitor (TG101209) led to normalization of the hematocrit and a reduction in splenomegaly. 5 These findings provide a strong rationale for JAK2 inhibition as a therapeutic approach for Chuvash polycythemia. We now report three patients with the disease who were treated with the JAK1 and JAK2 inhibitor ruxolitinib and who had symptomatic and hematologic improvement (Fig. 1A). Ruxolitinib was provided by Incyte, which was given access to the data and was allowed to review the manuscript before submission for publication; no specific modifications were requested by Incyte. Research samples were obtained through an institutional review board-Drs. Zhou, Knoche, and Engle contributed equally to this letter.
BMC Cancer
Background Although research has advanced the field of oncologic geriatrics with survivors to ass... more Background Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. Methods This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. Results Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with hea...
Blood, Nov 15, 2013
Chuvash polycythemia (CP) is a rare congenital polycythemia caused by mutations in the VHL gene. ... more Chuvash polycythemia (CP) is a rare congenital polycythemia caused by mutations in the VHL gene. Patients with CP present with erythrocytosis and are at high risk for thrombosis. Accordingly, CP patients have a significantly reduced lifespan. Currently, there are no proven therapies for CP. Studies demonstrating a potential benefit from phlebotomy or myelosuppressive agents have been lacking. CP exhibits features of both secondary and primary polycythemia. The former has been attributed to dysfunction of the mutant VHL protein leading to upregulation of HIFa under normoxic conditions, thereby resulting in increased erythropoietin (Epo) production. The latter is manifested by hypersensitivity of CP erythryoid progenitors to Epo in vitro, but the mechanism for this finding has not been fully explained. Recently, the VHL protein was shown to target phosphorylated JAK2 (pJAK2) for ubiquitin-mediated degradation. CP-associated VHL mutants were unable to degrade pJAK2, thereby leading to hyperactivation of downstream STAT signaling. In a CP mouse model, treatment with a JAK2 inhibitor led to normalization of hematocrit and reduction in splenomegaly. These findings provide a strong rationale for JAK2 inhibition as a therapeutic modality for CP. We now report preliminary data from two CP patients treated with the JAK inhibitor ruxolitinib. Baseline and on-treatment characteristics for the two patients are summarized in Table 1. Both patients were confirmed to be homozygous for the VHL R200W mutation. CP-01 first presented with erythrocytosis at 18 months. He was treated with intermittent phlebotomies and underwent a splenectomy at age 10. The patient had multiple thrombotic complications, including a deep vein thrombosis, pulmonary embolism, and portal vein thrombosis. He suffered from recurrent episodes of severe abdominal pain presumed to be related to his history of intra-abdominal thrombosis. The patient had a hemoglobin as high as 22.0 g/dL, and required four phlebotomies in a span of four weeks to achieve a hematocrit of 45.2% prior to initiating ruxolitinib. CP-01 was initiated on ruxolitinib at a starting dose of 10 mg orally twice daily and titrated up to the current dose of 20 mg twice daily. As of the most recent follow-up at 12 weeks, the patient has not required any phlebotomies since starting ruxolitinib and has not had any new episodes of abdominal pain. CP-02 was initially found to have erythrocytosis at the age of three. He was treated with intermittent phlebotomies but developed multiple thrombotic complications, including mesenteric vein thrombosis as well as a myocardial infarction at the age of 27. He also suffered from severe back pain presumed to be related to bone marrow expansion. The patient exhibited oscillations in his platelet count that were exacerbated after he underwent a splenectomy (platelet counts ranging between 7 x 109/L and 1900 x 109/L on a ∼30 day cycle). Periods of extreme thrombocytosis were associated with severe headaches requiring plateletpheresis. CP-02 was initiated on treatment with ruxolitinib, initially at a dose of 5 mg twice daily due to his periodic thrombocytopenia, and gradually titrated up to 20 mg twice daily. As of the most recent evaluation at 23 weeks, the patient reported significant improvement in his back pain, though he continued to require regular phlebotomies. His platelet count oscillations have improved dramatically, particularly at the current ruxolitinib dose of 20 mg twice daily (Figure 1). Strikingly, his lowest platelet count since starting ruxolitinib has been 187 x 109/L. This stabilization in his platelet count has been associated with an improvement in his headaches. To our knowledge, these two cases represent the first CP patients treated with a targeted inhibitor of JAK2. Both patients have experienced hematologic and symptomatic improvement, with no significant safety issues to date. These preliminary observations validate pre-clinical studies suggesting a role for JAK2 inhibition in CP. Correlative studies examining endogenous erythroid colony formation, JAK-STAT signaling, and inflammatory cytokine levels are ongoing. Disclosures: Oh: Incyte: Consultancy, Research Funding, Speakers Bureau. Off Label Use: Ruxolitinib for Chuvash polycythemia.
American Journal of Hematology, Oct 1, 2009
Streszczenie Zajęcie mięśnia sercowego jako pierwsza manifestacja rozwijającego się chłoniaka zło... more Streszczenie Zajęcie mięśnia sercowego jako pierwsza manifestacja rozwijającego się chłoniaka złośliwego jest stosunkowo rzadkim zjawiskiem. W niniejszej pracy opisano przypadek kliniczny 77-letnie-go mężczyzny, u którego wstępnie na podstawie badania echokardiograficznego zdiagnozowano patologiczną masę w obrębie lewego przedsionka objawiającą się klinicznie pod postacią stop-niowo narastającej duszności, dysfagii, odynofagii oraz gorączki. Patologiczna masa we-wnątrzsercowa była wstępnie traktowana jako skrzeplina i jako taka była leczona w warun-kach ambulatoryjnych za pomocą terapeutycznych dawek leków przeciwkrzepliwych. Przy przy-jęciu wykonano rezonans magnetyczny, w którym wykazano duży patologiczny twór w obrębie śródpiersia, który swój początek miał w obrębie przełyku i naciekał lewy przedsionek. Rentge-nowskie badanie kontrastowe przełyku z użyciem barytu uwidoczniło ubytek cienia o typowym wyglądzie ogryzka od jabłka, który obejmował dolną trzecią część przełyku. Na pods...
European journal of medical case reports, 2019
British Journal of Haematology, 2013
Histological transformation (HT) is a major cause of morbidity and mortality in patients with ind... more Histological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were identified. Treatments for HT included autologous stem-cell transplant (auto-SCT) (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto-SCT patients aged ≤60 years (n = 24), the 2-year OS was 74%. For nontransplanted patients aged ≤60 years (n = 19), the 2-year OS was 59%. The 2-year OS of patients na€ ıve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0Á03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era.
Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We des... more Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We describe the case of a 77-year-old man who had initially been diagnosed with a left atrial mass on an echocardiogram, presenting with progressive dyspnea, dysphagia, odynophagia and fevers. The cardiac mass had been managed as an outpatient with full anticoagulation for the suspicion of clot. On admission, cardiac magnetic resonance imaging revealed a large mediastinal mass invading the left atrium that originated from the oesophagus. A barium oesophagram revealed an apple core lesion involving the distal third of the oesophagus. A subsequent computed tomography scan demonstrated a large mediastinal soft tissue mass and paratracheal lymphadenopathy. A flexible upper endoscopy revealed an oesophageal mass that was approximately 10 cm in length, irregular at the margins, and with a very necrotic appearance. This was biopsied, revealing findings consistent with high grade diffuse large B cell ...
Blood
2669 Background The prognosis of histologic transformation (HT) of indolent…
European Journal of Medical Case Reports
Journal of Investigative Medicine High Impact Case Reports
Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the ... more Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies.
Blood, Nov 15, 2013
Chuvash polycythemia (CP) is a rare congenital polycythemia caused by mutations in the VHL gene. ... more Chuvash polycythemia (CP) is a rare congenital polycythemia caused by mutations in the VHL gene. Patients with CP present with erythrocytosis and are at high risk for thrombosis. Accordingly, CP patients have a significantly reduced lifespan. Currently, there are no proven therapies for CP. Studies demonstrating a potential benefit from phlebotomy or myelosuppressive agents have been lacking. CP exhibits features of both secondary and primary polycythemia. The former has been attributed to dysfunction of the mutant VHL protein leading to upregulation of HIFa under normoxic conditions, thereby resulting in increased erythropoietin (Epo) production. The latter is manifested by hypersensitivity of CP erythryoid progenitors to Epo in vitro, but the mechanism for this finding has not been fully explained. Recently, the VHL protein was shown to target phosphorylated JAK2 (pJAK2) for ubiquitin-mediated degradation. CP-associated VHL mutants were unable to degrade pJAK2, thereby leading to hyperactivation of downstream STAT signaling. In a CP mouse model, treatment with a JAK2 inhibitor led to normalization of hematocrit and reduction in splenomegaly. These findings provide a strong rationale for JAK2 inhibition as a therapeutic modality for CP. We now report preliminary data from two CP patients treated with the JAK inhibitor ruxolitinib. Baseline and on-treatment characteristics for the two patients are summarized in Table 1. Both patients were confirmed to be homozygous for the VHL R200W mutation. CP-01 first presented with erythrocytosis at 18 months. He was treated with intermittent phlebotomies and underwent a splenectomy at age 10. The patient had multiple thrombotic complications, including a deep vein thrombosis, pulmonary embolism, and portal vein thrombosis. He suffered from recurrent episodes of severe abdominal pain presumed to be related to his history of intra-abdominal thrombosis. The patient had a hemoglobin as high as 22.0 g/dL, and required four phlebotomies in a span of four weeks to achieve a hematocrit of 45.2% prior to initiating ruxolitinib. CP-01 was initiated on ruxolitinib at a starting dose of 10 mg orally twice daily and titrated up to the current dose of 20 mg twice daily. As of the most recent follow-up at 12 weeks, the patient has not required any phlebotomies since starting ruxolitinib and has not had any new episodes of abdominal pain. CP-02 was initially found to have erythrocytosis at the age of three. He was treated with intermittent phlebotomies but developed multiple thrombotic complications, including mesenteric vein thrombosis as well as a myocardial infarction at the age of 27. He also suffered from severe back pain presumed to be related to bone marrow expansion. The patient exhibited oscillations in his platelet count that were exacerbated after he underwent a splenectomy (platelet counts ranging between 7 x 109/L and 1900 x 109/L on a ∼30 day cycle). Periods of extreme thrombocytosis were associated with severe headaches requiring plateletpheresis. CP-02 was initiated on treatment with ruxolitinib, initially at a dose of 5 mg twice daily due to his periodic thrombocytopenia, and gradually titrated up to 20 mg twice daily. As of the most recent evaluation at 23 weeks, the patient reported significant improvement in his back pain, though he continued to require regular phlebotomies. His platelet count oscillations have improved dramatically, particularly at the current ruxolitinib dose of 20 mg twice daily (Figure 1). Strikingly, his lowest platelet count since starting ruxolitinib has been 187 x 109/L. This stabilization in his platelet count has been associated with an improvement in his headaches. To our knowledge, these two cases represent the first CP patients treated with a targeted inhibitor of JAK2. Both patients have experienced hematologic and symptomatic improvement, with no significant safety issues to date. These preliminary observations validate pre-clinical studies suggesting a role for JAK2 inhibition in CP. Correlative studies examining endogenous erythroid colony formation, JAK-STAT signaling, and inflammatory cytokine levels are ongoing. Disclosures: Oh: Incyte: Consultancy, Research Funding, Speakers Bureau. Off Label Use: Ruxolitinib for Chuvash polycythemia.
Conclusion: Botox appears to provide improvement in digital perfusion and pain reduction in patie... more Conclusion: Botox appears to provide improvement in digital perfusion and pain reduction in patients with Raynaud's syndrome when conservative management fails. Summary: Digital ulceration associated with Raynaud's syndrome is painful, difficult to treat, and frequently results in patient debilitation and chronic depression. Reports by Sycha and Van Beek have indicated potential benefit for patients with ischemic digits with local injection of botulinum toxin (
Schmaier/Concise Guide to Hematology, 2011
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Papers by Makiko Ban-Hoefen