Robin M. Reid

Rochester General Hospital

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Michael W. Becker

University of Rochester

Gordon L. Phillips

Atrium Health Wake Forest Baptist

Jane L. Liesveld

University of Rochester Medical Center

Laurie A. Milner

University of Rochester Medical Center

Jonathan W. Friedberg

University of Rochester

Lucy Wedow

University of Rochester Medical Center

Paul M. Barr

University of Rochester Medical Center

Mariam Mostafa

Galala University

Andrea Baran

University of Rochester Medical Center

Amir Mahmoud

Washington University in St. Louis

Cooperative Institutions

University of Rochester

University of Rochester Medical Center

Rochester General Hospital

Strong Memorial Hospital

Unity Health System

Cancer Institute (WIA)

Princess Margaret Cancer Centre

Ain Shams University

Memorial Sloan Kettering Cancer Center

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

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Relapsed Chronic Lymphocytic Leukemia Presenting with a Cardiac Mass: A Case Report

Blood (2022)

Amir Mahmoud Ali Abdelhay Mariam Mostafa Soon Khai Low Basant Eltaher

Supraclavicular lymph nodes

10.1182/blood-2022-166350

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Citations (0)

Outpatient administration of BEAM conditioning prior to autologous stem cell transplantation for lymphoma is safe, feasible, and cost‐effective

Cancer Medicine (2016)

Robin M. Reid Andrea Baran Jonathan W. Friedberg Gordon L. Phillips Jane L. Liesveld

Abstract High‐dose BEAM chemotherapy ( BCNU , etoposide, Ara‐C, and melphalan) followed by autologous hematopoietic stem cell transplantation is frequently used as consolidative therapy for patients with recurrent or refractory Hodgkin or non‐Hodgkin lymphoma. The BEAM regimen has traditionally been administered over 6 days in the hospital, with patients remaining hospitalized until hematologic recovery and clinical stability. In an effort to reduce the length of hospitalization for these patients, our institution has transitioned from inpatient ( IP ) to outpatient ( OP ) administration of BEAM conditioning. Here, we report the results of an analysis of the feasibility, cost, complications, and outcomes for the initial group of patients who received OP BEAM compared to a prior cohort of patients who received IP BEAM . Patient and disease characteristics were comparable for the two cohorts, as were engraftment kinetics. Length of hospital stay was reduced by 6 days for the OP cohort ( P < 0.001), resulting in a cost savings of more than $17,000 per patient. Fewer complications occurred in the OP cohort, including severe enteritis ( P = 0.01), organ toxicities ( P = 0.01), and infections ( P = 0.04). Overall survival rate up to 3 years posttransplant was better for the OP cohort ( P = 0.02), likely due to differences in posttransplant therapies. We conclude that OP administration of BEAM conditioning is safe and may offer significant advantages, including decreased length of hospitalization, reduced costs, decreased risks for severe toxicities and infectious complications, and likely improvement in patient satisfaction and quality of life.

Melphalan

Autologous stem-cell transplantation

10.1002/cam4.879

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Citations (20)

Outpatient Administration of High Dose BEAM Chemotherapy As Conditioning for Autologous Stem Cell Transplantation for Lymphoma Results in Fewer Infectious Complications and Improved Survival

Blood (2014)

Robin M. Reid Andrea Baran Paul M. Barr Michael W. Becker Steven H. Bernstein

Carmustine

Regimen

Melphalan

Autologous stem-cell transplantation

Chemotherapy regimen

10.1182/blood.v124.21.3984.3984

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Relapsed chronic lymphocytic leukemia with a cardiac mass: A case report

Radiology Case Reports (2023)

Amir Mahmoud Ali Abdelhay Mariam Mostafa Mohamed Salah Mohamed Zuhair Alam

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the USA. Extra-medullary disease is very rare and is not well characterized. In practice, clinically significant cardiac or pericardial involvement by CLL is extremely rare with only a few case reports in literature. We report a 51-year-old male patient with a past medical history of CLL in remission, who presented with fatigue, dyspnea on exertion, night sweats and left supraclavicular lymphadenopathy. Laboratory investigations were notable for leukopenia and thrombocytopenia. Due to high suspicion of an underlying malignant process, a full body computerized tomography (CT) scan was obtained and showed an 8.8 cm soft tissue mass-like lesion occupying the majority of the right atrium and extending into the right ventricle, with probable pericardial involvement. Enlarged left supraclavicular and mediastinal lymph nodes were also present and had a mild mass effect on the traversing left internal thoracic artery and left pulmonary artery. A transesophageal echocardiogram and cardiac magnetic resonance imaging (MRI) were done to better characterize the cardiac mass. They confirmed a large infiltrating mass (measuring 10 × 7.4 cm) in the right atrium and ventricle, extending into the inferior vena cava inferiorly and coronary sinus posteriorly. A left supraclavicular excisional lymph node biopsy was performed and histopathology was consistent with Small Lymphocytic Lymphoma (SLL)/CLL. This case represents one of the few known cases of cardiac extramedullary-CLL presenting with an isolated cardiac mass. Further studies are needed to characterize the course of the disease, prognosis and optimum management along with the role of surgery.

Supraclavicular lymph nodes

Palpitations

10.1016/j.radcr.2023.02.051

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Use of eltrombopag, a thrombopoietin receptor agonist, in post‐transplantation thrombocytopenia

American Journal of Hematology (2012)

Robin M. Reid John M. Bennett Michael W. Becker Yuhchyau Chen Laurie A. Milner

Persistent thrombocytopenia after stem cell transplantation can lead to increased morbidity and mortality [1, 2]. The underlying causes are often multifactorial in this patient population [3, 4]. In autologous transplantation, thrombocytopenia is usually a result of poor engraftment or a sign of impending disease relapse. In allogeneic stem cell transplantation, the etiology is often more complex with engraftment deficits, medication effects, graft versus host disease (GVHD), and other immunologic processes potentially contributing. Eltrombopag is an orally available nonpeptide thrombopoietin (TPO) receptor agonist which interacts with the transmembrane domain of the receptor on bone marrow megakaryocytes and upstream progenitor/stem cells. It has been studied in patients with chronic idiopathic thrombocytopenic purpura [5] and in patients with thrombocytopenia secondary to hepatitis C infection [6]. Unlike the case with recombinant human TPO, its use has not been associated with anti-platelet antibody production [7]. We report two cases of post-transplantation thrombocytopenia, one allogeneic and one autologous, where eltrombopag was given to treat prolonged thrombocytopenia. The use of eltrombopag in these two cases was effective in elevating platelet counts to levels that eliminated the need for platelet transfusions. A 63-year-old female with hypertension, congestive heart failure, and chronic obstructive pulmonary disease was diagnosed with acute myelogenous leukemia (AML) with positive FLT3-internal tandem duplication (ITD) mutation status and normal cytogenetics. She initially presented with anemia, superficial thrombophlebitis in the lower and upper extremities, and a left lower extremity deep venous thrombosis. She was started on low molecular weight heparin, and an inferior vena cava filter was placed. She underwent induction chemotherapy with idarubicin and cytarabine. She had delay in count recovery and marrow done on Days 14 and 21 showed residual blasts, so she was reinduced. Subsequent to her original diagnostic specimen, all marrows were FLT3 ITD negative. After a second induction chemotherapy with cytarabine and idarubicin, the marrow showed 5% blasts, and she was given two courses of high-dose cytarabine with marrow response and normalization of blood counts. Seven months later, a marrow showed recurrence of AML. She was subsequently treated with six cycles of decitabine. She required intermittent red cell transfusions but no platelet or antibiotic support during decitabine therapy. Again at one and half years after her original diagnosis, marrow showed residual AML with extensive fibrosis and some multilineage dysplasia. The Jak2 mutation analysis was negative, and the cytogenetics remained normal. The patient remained red cell transfusion dependent with resultant iron overload, and she developed splenomegaly. She was placed on hydroxyurea and deferasirox. She developed an upper extremity DVT thought to be catheter related and was placed on low molecular weight heparin chronically. Due to the refractory nature of the patient's leukemia and the subsequent marrow fibrosis, a reduced-intensity stem cell transplantation was recommended. A 10/10 HLA matched female unrelated donor was secured. At 1.8 years after the original diagnosis, the patient received a conditioning regimen consisting of extracorporeal photopheresis, pentostatin, and 600 cGy total body irradiation. The patient was seropositive for cytomegalovirus (CMV), whereas the donor was seronegative for CMV. Tacrolimus and mycophenylate mofetil were utilized for GVHD prophylaxis. She received 7 × 106 CD34+ peripheral blood stem cells per kilogram from her donor. The patient had no count recovery by Day +29 after stem cell infusion, and a marrow biopsy on Day +31 confirmed marked hypocellularity and only 44% donor chimerism. Her counts continued to slowly recover, and by Day +45, peripheral blood chimerism analysis showed 99% donor contribution. The patient remained profoundly thrombocytopenic, requiring twice per day platelet transfusions and epsilon aminocaproic acid (EACA) to treat mucosal bleeding, as well as RBC transfusions. Eventually, she tolerated every other day platelet transfusion and EACA was discontinued. Potentially myelosuppressive medications such as mycophenylate mofetil and trimethoprim-sulfamethoxazole were discontinued. Because of persistent cytopenias and transfusion needs, a second stem cell infusion (3.7 × 106 CD34+ cells/kg) from the same donor was administered on Day +120 without re-conditioning. The patient developed Grade 1 graft vs. host disease of the skin, but this resolved with increased tacrolimus. Despite the second stem cell infusion, the platelet count remained <10,000/uL. The spleen was not palpable. Platelet-related antibody (PRA), anti-HLA antibodies, and platelet factor 4 (PF4) assays were negative. Because of her extreme dependence on platelet transfusions, the decision was made to begin eltrombopag on Day +140 at 50 mg/day. Concurrently, she developed reactivation of CMV and was started on therapeutic dosing of both valganciclovir and foscarnet. She initially became more cytopenic, and marrow showed hypocellularity with no residual AML. By approximately 2 weeks after beginning eltrombopag, the patient became platelet transfusion independent with platelets reaching the 30,000/uL range (Fig. 1). Her CMV titers became positive again, and despite valganciclovir administration, platelet counts remained in the 20,000–40,000/uL range without the need for transfusion support. Eltrombopag was discontinued after approximately 6 weeks because of the underlying history of marrow fibrosis and the adequacy of platelet counts to prevent severe bleeding risk or transfusion need. The patient remained red cell transfusion dependent despite treatment with erythropoietin. By Day +240, the patient started to demonstrate blasts in the peripheral blood, and she was transitioned to hospice care. She died approximately 270 days after her original stem cell infusion. Bone marrow biopsy images showing reticulin stain with a 3+ reaction (A) and H&E stain (B) showing numerous small atypical megakaryocytes with dense fibrosis, at transplant day 224, marked on graph. This was typical of the marrow throughout the disease course when the AML was quiescent. Final magnification 400×. C: Associated graph showing platelet counts (blue) in relation to time of initiation of eltrombopag (pink) and platelet transfusions (green) marked starting at day of the allogeneic bone marrow transplant. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] A 42-year-old female with prior history of ITP previously treated with steroids and intravenous immune globulin (IVIG) was diagnosed with AML. Platelet counts prior to the diagnosis of AML were approximately 100,000/uL. Cytogenetics showed (47 X, X inv (16) (p13; p22) +22) in three metaphases, and she was treated with standard daunorubicin and cytarabine. Morphologic remission was achieved and confirmed by fluorescence in situ hybridization (FISH) evaluation, which showed no deletion of the core binding factor—beta (CBFβ) gene, and she received consolidation with high-dose cytarabine for four cycles. Relapse occurred 13 months after original diagnosis, and she was induced into a second remission with FLAG chemotherapy (fludarabine, high-dose cytarabine, and granulocyte colony stimulating factor (filgrastim)). After one additional cycle of high-dose cytarabine consolidation, autologous stem cells were collected after filgrastim administration. Registry searches throughout her leukemia course revealed no unrelated donors of suitable HLA match grade, and no 4/6 or greater cord unit matches were found due to a rare DRβ1 allele. At the time of relapse, G-banding metaphases were 46(X, X), but FISH had shown a split of CBFβ in 12/200 cells. The patient had conditioning with busulfan (0.8 mg/kg for 16 doses) and cyclophosphamide (60 mg/kg for 2 doses), and she had 2.35 × 106 CD34+ cells/kg infused. Her neutrophils engrafted at Day +12, but the platelets did not engraft. She required frequent transfusions of both red cells and platelets as well as erythropoietin support. Bone marrow biopsies performed 2, 5, 8, and 11 months post-autologous stem cell infusion all showed hypocellularity and the absence of megakaryocytes with no evidence for leukemia. FISH remained negative for split of CBFβ. Eventually, the patient became red cell transfusion independent, and she continued to require several platelet transfusions per week. Chelation attempts were begun with deferoxiamine and later deferasirox due to elevated ferritin levels. The patient had significant vaginal bleeding necessitating hormone replacement and the use of EACA. She eventually required an endometrial hydroablation. Because of the persistent thrombocytopenia, eltrombopag 50 mg/day was started at approximately 14 months after the autologous stem cell transplantation. Two weeks after beginning eltrombopag, the patient's platelet count remained consistently above 10,000/uL, and she became platelet transfusion independent (Fig. 2). Marrow biopsies performed after 4 and 12 months of eltrombopag exposure showed no significant fibrosis (1+) and the presence of adequate megakaryocytes (Fig. 2). There was no evidence of residual leukemia, and cytogenetics remained normal. At the time of publication (28 months after stem cell infusion), the eltrombopag has been stopped, and the platelet count has remained at approximately 40,000/uL. The image in (A) shows normocellular marrow with no megakaryocytes noted prior to eltrombopag (day 120 after stem cell transplant). The image in (B) reveals normocellular marrow with normal numbers of megakaryocytes (day +540 after stem cell transplant), four months following initiation of eltrombopag; both H&E stains with final magnification 400×. C: Associated graph showing platelet counts in relation to time with platelet transfusions marked. The autograft occurred in 3/09. The line indicates duration of eltrombopag administration. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] The first case demonstrates the complexity of thrombocytopenia in allogeneic stem cell transplantation patients. Engraftment was poor, and mycophenylate and trimethoprim-sulfamethoxazole, as well as other potentially myelosuppressive medications were administered [8]. Her spleen was not enlarged post-transplantation and she had no evidence for a microangiopathic process. Given her ongoing reticulin fibrosis, an unfavorable environment might have contributed to the slow donor cell engraftment. GVHD itself is associated with thrombocytopenia including tissue injury with cytokine release, the production of transforming growth factor-beta, and low levels of TPO [3], but in this case, only Grade I–II skin GVHD was transiently documented, so it was unlikely that GVHD was a major contributor to the thrombocytopenia. Reactivation of CMV infection is a common cause of thrombocytopenia in the post-transplant setting, and this might have contributed to some of the later thrombocytopenia. The valganciclovir may also have suppressed the platelets, and in fact, with its second course, it suppressed the platelet count from the peak noted during eltrombopag therapy. This first case serves to illustrate that eltrombopag or similar agents may serve to elevate platelet counts in the face of multiple contributors to reduced platelet production. The dose and duration of eltrombopag exposure were minimized because of the prior history of marrow fibrosis, although it might be argued that after an allograft, the original hematopoietic clone which incited the myelofibrosis should have been eliminated. This patient had a relapse of her disease later, well after discontinuation of the eltrombopag. It was unlikely that eltrombopag contributed to this relapse, as it has been found to inhibit AML blasts [9]. In the second case, the post-transplantation thrombocytopenia was most likely related to poor engraftment of megakaryocytes in the autologous stem cell infusion setting. In this patient, all post-transplantation marrows showed the absence of megakaryocytes making reactivation of ITP unlikely, and the application of eltrombopag improved platelet counts and resulted in increased megakaryocytes in the bone marrow. Significant bone marrow fibrosis was not noted in this case when the dose and duration of eltrombopag were minimized. Both cases presented here represent situations in which TPO receptor mimetics may be of utility in post-transplant situations. Systematic trials of such agents in post-transplantation settings would be of interest, and romiplostim, another TPO receptor agonist, has been reported in a small series of patients to improve platelet recovery after allogeneic stem cell transplantation in secondary failure states [10]. Authors thank Gary Roloff for aid in graph preparation and Elva Mikk for aid in manuscript submission. Robin Reid*, John M. Bennett , Michael Becker*, Yuhchyau Chen , Laurie Milner*, Gordon Phillips*, Jane Liesveld*, * Department of Internal Medicine, University of Rochester Medical Center, Rochester, New York, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, Department of Radiation Oncology, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.

Thrombopoietin receptor

Eltrombopag

10.1002/ajh.23225

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Management of marginal zone lymphoma.

PubMed (2013)

Robin M. Reid Jonathan W. Friedberg

MZL comprises three different entities that require integration of clinical and pathologic features to make a diagnosis. Treatment is chosen and initiated on the basis of presentation, symptoms, and underlying subtype.

Presentation (obstetrics)

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Citations (10)