Jiasheng Wang, John Doran
Cytokine release syndrome (CRS) has been increasingly recognized in various conditions including the coronavirus disease 2019 (COVID-19). It is not only associated with systemic inflammatory symptoms, but also hematological complications such as coagulopathy. CRS can affect various components of the...
Ibrahim N. Muhsen, David Shyr, Anthony D. Sung, Shahrukh K. Hashmi
The use of machine learning (ML) and deep learning (DL) methods in hematology includes diagnostic, prognostic, and therapeutic applications. This increase is due to the improved access to ML and DL tools and the expansion of medical data. The utilization of ML remains limited in clinical practice, with...
Treen Carson Michael Morris, Mary B. Drake, Paul J. Kettle, Tracey McGuigan, Maeve Leahy, Michael O’Dwyer, Helen Enright, Tanya O’Shea, Rakesh Popat, Heather E. Oakervee, Kwee Yong, Jamie D. Cavenagh, David A. Cairns, Alberto Alvarez-Iglesias, Gordon Cook
When the bortezomib [PS341], adriamycin and dexamethasone (PAD) regimen was first evaluated, the response rate in untreated patients was much superior to that elicited by conventional chemotherapeutic agents. We demonstrated the efficacy of PAD in relapsed or refractory patients by comparing the response...
Elena E. Solomou, Christina Salamaliki, Maria Lagadinou
Isolated neutropenia without anemia or thrombocytopenia is a common clinical problem. The etiology of neutropenia may vary from transient bone marrow suppression, caused by self-limited viral illnesses, to previously undiagnosed congenital syndromes or serious systemic diseases. Consequently, determining...
Mohamad Mohty, Arnon Nagler, Bipin Savani
Pages: 1 - 1
Mohamad Mohty, Arnon Nagler, Bipin Savani
Pages: 1 - 1
Mohamed A. Kharfan-Dabaja, Naveen Pemmaraju, Mohamad Mohty
Pages: 2 - 9
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from precursors of plasmacytoid dendritic cells. There is no established standard therapy for BPDCN and the efficacy of conventional chemotherapy is limited, with an anticipated median overall...
Abraham S. Kanate, Arnon Nagler, Bipin Savani
Pages: 2 - 4
Due to the increasingly strict word/character restrictions enforced by most scientific publications, we identified a need for a master document illustrating the “Scientific Methods” that may be applicable to the majority of observational and registry-based studies in hematopoietic cell transplantation...
Cosmin Tegla, Jun Choi, Maher Abdul-Hay, Frank Cirrone, Kelli Cole, A Samer Al-Homsi
Pages: 5 - 12
Graft-versus-host disease (GvHD) in its acute and chronic forms continues to represent a significant barrier to the success and wide-applicability of blood and marrow transplantation as a potentially curative treatment modality for a number of benign and malignant blood conditions. Presently, calcineurin...
Pages: 10 - 18
The therapeutic paradigm for treatment of acute myeloid leukemia (AML) is rapidly changing with the advent of a new generation of drugs targeting diverse aspects of leukemogenesis. Whereas standard treatment for AML until recently consisted of a classic chemotherapy backbone, the incorporation of novel...
Pages: 13 - 17
Despite considerable advances in our understanding of the molecular and epigenetic underpinnings of the myelodysplastic syndromes (MDS), this diverse group of myeloid neoplasms remains a significant clinical challenge. Considerable barriers to timely development of effective therapy include the diverse...
Oluwadunni E. Emiloju, Rashmika Potdar, Vinicius Jorge, Sorab Gupta, Gabor Varadi
Pages: 18 - 26
Apart from peripheral blood stem cell (PBSC), umbilical cord blood (UCB) is now a recognized source of stem cells for transplantation. UCB is an especially important source of stem cells for minority populations, which would otherwise be unable to find appropriately matched adult donors. UCB has fewer...
Rashmika R. Potdar, Sorab Gupta, Sebastian Giebel, Bipin N Savani, Gabor Varadi, Arnon Nagler, Slawomir Blamek
Pages: 19 - 27
Acute myeloid leukemia and acute lymphoblastic leukemia are the most common indications for allogeneic hematopoietic stem cell transplantation. Total body irradiation (TBI) is an important part of conditioning regimens. TBI-based regimens offer advantages in sanctuary sites but are associated with significant...
Bogdan Popescu, Sheenu Sheela, Julie Thompson, Sophia Grasmeder, Therese Intrater, Christin B. DeStefano, Christopher S. Hourigan, Catherine Lai
Pages: 27 - 31
Therapy for those with relapsed or refractory acute myeloid leukemia is suboptimal. Studies have suggested that timed sequential salvage combination cytotoxic chemotherapy may be particularly useful for that indication. We report here a series of ten such adult patients treated sequentially at a single...
Roni Shouval, Mika Geva, Arnon Nagler, Ilan Youngster
Pages: 28 - 35
The growing understanding of the bidirectional relationship between the gastrointestinal (GI) microbiome and the immune system has opened up new avenues for treatment of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) is the transfer of stool from a donor to a recipient who harbors...
Jacques Mario Azzi, Doyun Park, Maher Abdul-Hay, Kelli Cole, Frank Cirrone, Maxim Kreditor, A. Samer Al-Homsi
Pages: 32 - 34
Human herpesvirus-6 (HHV-6) is a highly prevalent virus that establishes lifelong latency in human hosts. Symptomatic HHV-6 reactivation rarely occurs in immunocompetent individuals and is best described in immunosuppressed patients such as recipients of bone marrow transplants (BMT). In that setting,...
Kristian T. Andersen, Maja Hinge, Agoston Gyula Szabo, Erik Segel, Tina Ormstrup, Paw C. Holdgaard, Niels Pallisgaard, Gitte Kerndrup, Torben Plesner
Pages: 35 - 39
Iskra Pusic, Steven Z. Pavletic
Pages: 36 - 44
The lack of standardized criteria for measuring therapeutic response has been a major obstacle to the development of therapeutic trials in chronic graft-versus-host disease (cGvHD). Nevertheless, recent advances have been made in understanding of the biology and pathophysiology of cGvHD, as well as establishing...
Mohamad Mohty, Arnon Nagler, Bipin Savani
Pages: 41 - 42
Jacob Shreve, Aziz Nazha
Pages: 43 - 48
Myelodysplastic syndromes (MDSs) are potentially devastating monoclonal deviations of hematopoiesis that lead to bone marrow dysplasia and variable cytopenias. Predicting severity of disease progression and likelihood to undergo acute myeloid leukemia transformation is the basis of treatment strategy....
Marta Palomo, Maribel Diaz-Ricart, Enric Carreras
Pages: 45 - 51
The goal of this review is to look at the role of endothelial damage and dysfunction in the initiation and development of early complications that appear after hematopoietic cell transplantation (HCT). These early complications share overlapping clinical manifestations and the suspicion of underlying...
Samuel Cytryn, Maher Abdul-Hay
Pages: 49 - 58
Allogeneic hematopoietic cell transplant (Allo-HCT) is a potentially curative therapy for many malignant and nonmalignant hematological diseases. However, a suitable human leukocyte antigens (HLAs)-matched donor may not be available when the patient is in urgent need of a stem cell transplant. This challenge...
Elena E. Solomou
Pages: 52 - 57
“Bone marrow failure” encompass all the conditions and syndromes in which there are qualitative or quantitative disorders of one or more lineages (erythroid, myelomonocytic, and/or megakaryocytic). A few years ago, the pathophysiology of these syndromes was completely unknown. Today we have better knowledge...
Ali Bazarbachi, Myriam Labopin, Giorgia Battipaglia, Azedine Djabali, Edouard Forcade, William Arcese, Gerard Socié, Didier Blaise, Joerg Halter, Sabine Gerull, Jan J. Cornelissen, Patrice Chevallier, Johan Maertens, Nicolaas Schaap, Jean El-Cheikh, Jordi Esteve, Arnon Nagler, Mohamad Mohty
Pages: 58 - 74
Acute myeloid leukemia (AML) with FLT3-mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with FLT3-mutated AML allografted between 2010 and 2015 from a matched related (40%),...
Sarah A. Bird, Graham H. Jackson, Charlotte Pawlyn
Pages: 59 - 68
Multiple myeloma, the second most common hematological malignancy worldwide, has demonstrated dramatic improvements in outcome in the last decade. In newly diagnosed patients, induction chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care. After ASCT, the majority...
Ehsan Shabbir, Umar Farooq, Burhan Yanes, Margarida Magalhaes-Silverman
Pages: 69 - 73
Graft versus host disease (GVHD) of the gut is associated with significant morbidity and mortality after allogeneic hematopoietic cell transplant (allo-HCT). No guidelines exist regarding repeat endoscopy after failure of first-line treatment with steroids. We aimed to study if repeat endoscopic biopsy...
M. Remberger, B. Grønvold, M. Ali, J. Mattsson, T. Egeland, K. U. Lundin, A. Myhre, I. Abrahamsen, D. Heldal, I. Dybedal, G. E. Tjønnfjord, T. Gedde-Dahl, Y. Fløisand
Pages: 74 - 81
The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological...
Rishabh Gupta, Ujjawal Savani, Katie Gatwood, Katie Culos
Pages: 75 - 77
Pages: 79 - 84
Application of immunotherapeutic modalities changed paradigms in the treatment of hematologic malignancies, with regards to drug manufacturing, treatment protocols, short- and long-term toxicities. FDA-approved therapies, including blinatumomab, tisagenlecleucel, and axicabtagene ciloleucel, target T...
Raheel Iftikhar, Qamar un Nisa Chaudhry, Tariq Mehmood Satti, Syed Kamran Mahmood, Tariq Ghafoor, Ghassan Umair Shamshad, Nighat Shahbaz, Mehreen Ali Khan, Tariq Azam Khattak, Jahanzeb Rehman, Muhammad Farhan, Saima Humayun, Humera Haq, Syeda Ammaara Anwaar Naqvi, Faiz Anwer, Humayoon Shafique Satti, Parvez Ahmed
Pages: 82 - 91
Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning...
Enrico Maffini, Francesco Saraceni, Francesco Lanza
Pages: 85 - 93
The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very poor outcome. Allogeneic hematopoietic cell transplantation...
Mohamad Mohty, Florent Malard, Ali Bazarbachi
Pages: 92 - 93
Katie Culos, Michael Byrne
Pages: 94 - 100
Patients with high-risk myeloid neoplasms, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are offered allogeneic hematopoietic cell transplantation (alloHCT) to improve the likelihood of long-term disease control. More than 50% of patients with high-risk disease will relapse...
Amy P. Gabbard, Garrett S. Booth
Pages: 95 - 100
Cold agglutinin disease (CAD) is an uncommon form of cold autoimmune hemolytic anemia (AIHA). It should be considered in the differential diagnosis of elderly patients with unexplained chronic anemia presenting with or without cold-induced symptoms in the extremities, such as the fingers, ears, and nose....
Naomi Fei, Nilay Shah, Aaron Cumpston, Sijin Wen, Kelly G. Ross, Michael Craig, Abraham S. Kanate
Pages: 101 - 104
Varicella zoster virus (VZV) reactivation after autologous hematopoietic cell transplantation (auto-HCT) may be observed in a quarter of patients. Currently, prophylactic use of acyclovir 800 mg twice daily or valacyclovir 500 mg twice daily is recommended for prophylaxis against VZV reactivation for...
Uttam K. Rao, Brian G. Engelhardt
Pages: 101 - 108
Patients undergoing allogeneic hematopoietic cell transplantation (HCT) are at risk for numerous acute and long-term complications from this procedure. Post-transplant diabetes mellitus (PTDM) is a common but under-recognized problem. Similar to graft-versus-host disease (GVHD), new-onset diabetes is...
Maria Queralt Salas, Arjun Datt Law, Wilson Lam, Zeyad Al-Shaibani, David Loach, Dennis (Dong Hwan) Kim, Fotios V. Michelis, Santhosh Thyagu, Rajat Kumar, Jeffrey Howard Lipton, Jonas Mattsson, Auro Viswabandya
Pages: 105 - 113
Haploidentical stem cell transplantation (haploSCT) has greatly improved access to curative treatment for myeloid malignancies in patients without suitable matched sibling/unrelated donors. We investigated the safety and efficacy of haploSCT after reduced intensity conditioning (RIC) with anti-thymocyte...
Natasha A. Jain, Marcus Y. Chen, Sujata Shanbhag, Prathima Anandi, Xin Tian, Sawa Ito, Priyanka A. Pophali, Kimberly Doucette, Robert Q. Le, Upneet Chawla, Eleftheria Koklanaris, Richard W. Childs, A. John Barrett, Minoo Battiwalla
Pages: 109 - 116
Long-term allogeneic hematopoietic cell transplant (allo-HCT) survivors suffer an elevated risk of coronary heart disease (CHD). We conducted a prospective, nonrandomized, cross-sectional study to screen asymptomatic survivors at a single allo-HCT center using cardiac computed tomography (CT) involving...
Raja Pramanik, Harish Kancharla, Sameer Bakhshi, Atul Sharma, Ajay Gogia, Prabhat Malik, Ranjit Kumar Sahoo, Atul Batra, Sanjay Thulkar, Lalit Kumar
Pages: 114 - 119
Engraftment syndrome (ES) is a clinical syndrome that occurs in the early neutrophil recovery phase following hematopoietic stem cell transplant (HSCT). Although also described for allogenic HSCT, it is basically diagnosed in the context of autologous HSCT. We retrospectively reviewed 171 consecutive...
Bhagirathbhai Dholaria, Yenny Alejandra Moreno Vanegas, Nancy Diehl, Aaron C. Spaulding, Sue Visscher, Han W. Tun, Sikander Ailawadhi, Prakash Vishnu
Pages: 117 - 124
Dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA.R-EPOCH) is used for upfront treatment of high-risk diffuse large B cell lymphoma (DLBCL). In this study, we compared the outcomes in patients with high-risk DLBCL who received frontline rituximab, cycophosphamide,...
Raffaella Greco, Maria Chiara Barbanti, Nicasio Mancini, Laura Infurnari, Renée Pasciuta, Alessandra Forcina, Chiara Oltolini, Gabriele Casirati, Daniele Mannina, Fabio Giglio, Carlo Messina, Mara Morelli, Francesca Lorentino, Sara Mastaglio, Tommaso Perini, Luca Vago, Paolo Scarpellini, Matteo Giovanni Carrabba, Maria Teresa Lupo Stanghellini, Sarah Marktel, Andrea Assanelli, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Massimo Clementi, Fabio Ciceri
Pages: 120 - 123
Infections are a major cause of morbidity and mortality in hematological patients. We prospectively tested a new molecular assay (Verigene®) in 79 consecutive hematological patients, with sepsis by gram-negative bacteria. A total of 82 gram-negative microorganisms were isolated by blood cultures, of...
Katie S. Gatwood, Bipin N. Savani
Pages: 124 - 126
Meghali Goswami, Katherine E. Lindblad, Rahul Ramraj, Pradeep K. Dagur, Julie Thompson, J. Philip McCoy, Christopher S. Hourigan
Pages: 125 - 128
Brian D. Adkins, Bipin N. Savani, Garrett S. Booth
Pages: 127 - 133
Sickle cell disease patients are commonly treated at transfusion medicine services, and understanding of the hepatic manifestations of the disease is key for optimal management, specifically, in individuals presenting with sickle cell intrahepatic cholestasis (SCIC). SCIC represents a rare, severe hepatic...
Federica Ricci, Serena Balducci, Francesca Guerrini, Susanna Grassi, Elena Ciabatti, Claudia Baratè, Maria Immacolata Ferreri, Cecilia Giuliani, Angelo Valetto, Mario Petrini, Sara Galimberti
Pages: 129 - 131
Anna Suska, David H. Vesole, Jorge J. Castillo, Shaji K. Kumar, Hari Parameswaran, Maria V. Mateos, Thierry Facon, Alessandro Gozzetti, Gabor Mikala, Marta Szostek, Joseph Mikhael, Roman Hajek, Evangelos Terpos, Artur Jurczyszyn
Pages: 133 - 142
Plasma cell leukemia (PCL) is an aggressive hematological malignancy characterized by an uncontrolled clonal proliferation of plasma cells (PCs) in the bone marrow and peripheral blood. PCL has been defined by an absolute number of circulating PCs exceeding 2.0 × 109/L and/or >20% PCs in the total...
Ugur Sahin, Meral Beksac
Pages: 134 - 141
Our understanding on the mechanisms of graft versus tumor/leukemia (GvT/GvL) and graft versus host (GvH) effects has tremendously evolved within the past decades. During the search for a mechanism that augments GvT/GvL without increasing GvH effects, natural killer (NK) cells have clearly attracted attention....
Mohammad Shahrukh Tanweer, Mahmoud Aljurf, Bipin N. Savani, Perviz K. Iqbal, Shahrukh Hashmi
Pages: 142 - 153
Female recipients of hematopoietic cell transplant (HCT) may develop lower genital tract (LGT) dysplasia or new malignancies. A comprehensive systematic review to delineate the occurrence and risk factors for post-HCT LGT precancer and cancer in women was conducted via electronic search of the Cochrane...
Pierre Brissot, Eolia Brissot
Pages: 143 - 148
Major advances in the understanding of genetic iron overload have led to a clarification of the nosology and terminology of the related diseases. The term hemochromatosis should be reserved to the entities where iron overload is related to hepcidin deficiency or hepcidin resistance. The diagnosis of...
Anas Zahid, Elizabeth L. Siegler, Saad S. Kenderian
Pages: 149 - 155
T cells genetically engineered with chimeric antigen receptors (CART) have become a potent class of cancer immunotherapeutics. Numerous clinical trials of CART cells have revealed remarkable remission rates in patients with relapsed or refractory hematologic malignancies. Despite recent clinical success,...
Elisa Roldan, Miguel Angel Perales, Pere Barba
Pages: 154 - 160
The success of allogeneic stem cell transplant is hampered by the development of acute and chronic graft-versus-host disease (GvHD) which has direct impact on treatment-related mortality and morbidity. As a result, T cell depletion through positive selection of CD34+ cells has emerged as a promising...
Sejal Morjaria, Allen W. Zhang, Sohn Kim, Jonathan U. Peled, Simone Becattini, Eric R. Littmann, Eric. G. Pamer, Michael C. Abt, Miguel-Angel Perales
Pages: 156 - 164
Background: Monocytes are an essential cellular component of the innate immune system that support the host’s effectiveness to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations...
Sandhya R. Panch, Opal L. Reddy, Katherine Li, Thejaswi Bikkani, Anusha Rao, Swathi Yarlagadda, Steven Highfill, Daniel Fowler, Richard W. Childs, Minocher Battiwalla, John Barrett, Andre Larochelle, Crystal Mackall, Nirali Shah, David F. Stroncek
Pages: 161 - 167
Cell separation technologies play a vital role in the graft engineering of hematopoietic cellular fractions, particularly with the rapid expansion of the field of cellular therapeutics. The CliniMACS Plus Instrument (Miltenyi Biotec) utilizes immunomagnetic techniques to isolate hematopoietic progenitor...
Joseph A. Wilson, Stephanie Hayden, Alexander Asamoah, Vivek R. Sharma, David C. Jennings, Ashok B. Raj
Pages: 165 - 167
Emicizumab is increasingly the front-line treatment for patients with Hemophilia A with or without inhibitors. Rhabdomyolysis is a syndrome of muscle necrosis and release of intracellular muscle constituents into the circulation. Creatine kinase (CK) levels are typically markedly elevated, and muscle...
Tran-Der Tan, Lun-Wei Chiou, Mau-Ching Wu, Jia-Shing Wu, Ming-Yuan Lee, Yu-Yi Huang, Shing-Su Chen
Pages: 168 - 172
We retrospectively analyzed the impact of initial positron emission tomography and computed tomography (PET-CT) complete remission (CR) and time to next treatment (TTNT) on patient outcome in follicular lymphoma. Between 2002 and 2014, 150 patients could be evaluated for treatment response and long-term...
Agoston Gyula Szabo, Katrine Fladeland Iversen, Flemming Schønning Rosenvinge, Sören Möller, Torben Plesner
Pages: 168 - 172
James Bussel, Oriana Miltiadous
Pages: 173 - 179
The differences in diagnosis and management between immune thrombocytopenia (ITP) and leukemia are striking. Leukemia diagnosis and management have evolved substantially over the past 30 years and are now relatively precise. The tendency for leukemic cells to be the overwhelming majority of circulating...
Yongxian Hu, Linqin Wang, Qu Cui, Elaine Tan Su Yin, Hengwei Wu, Arnon Nagler, He Huang
Pages: 173 - 175
Juliana Matthews, Dwight Eplin, Bipin Savani, Barbara Gisella Carranza Leon, Leslee Matheny
Pages: 180 - 188
Hematopoietic stem cell transplantation (HSCT) has become a potentially curative therapy for an increasing number of malignant and non-malignant conditions. As survival rates continue to improve, the focus of patient care has shifted from managing not only immediate but also long-term complications....
Francesca Bonello, Giusy Cetani, Luca Bertamini, Francesca Gay, Alessandra Larocca
Pages: 189 - 200
The introduction of novel agents, characterized by favorable toxicity profiles and higher manageability compared to conventional drugs employed in the past, has considerably changed the treatment paradigm for multiple myeloma. Continuous therapy currently represents the standard approach for myeloma...
Zachariah DeFilipp, Nalu Navarro-Alvarez, Shuli Li, Alec R. Andrews, Ariel Johnson, Yi-Bin Chen, Vincent T. Ho, Jerome Ritz, Thomas R. Spitzer, Christene A. Huang
Pages: 201 - 204
Galectin-3 is a beta-galactoside-binding lectin with an established association to inflammatory and fibrotic conditions. We investigated galectin-3 levels in 68 recipients of allogeneic hematopoietic cell transplantation (HCT) to look for associations with chronic graft-versus-host disease (cGVHD). Plasma...
Lalit Kumar, Santosh Kumar Chellapuram, Ramavat Dev, Ankur Varshneya, Satyajit Pawar, Aparna Sharma, Anjali Mookerjee, Ranjit Kumar Sahoo, Prabhat Singh Malik, Atul Sharma, Ritu Gupta, Omdutta Sharma, Ahitagni Biswas, Rakesh Kumar, Sanjay Thulkar, Sauumyaranjan Mallick
Pages: 205 - 219
We investigated the impact of renal impairment (RI) on the outcome in multiple myeloma (MM) patients following induction and autologous stem cell transplantation (ASCT). Among 349 patients who received a first ASCT for MM, 86 (24.6%) had RI at diagnosis, defined as estimation of glomerular filtration...
Agoston Gyula Szabo, Katrine Fladeland Iversen, Sören Möller, Torben Plesner
Pages: 220 - 228
In this retrospective study we reviewed the clinical course of every patient with multiple myeloma treated from 2006 to 2016 at Vejle Hospital: 303 patients with a median age of 69 years at diagnosis received a median of four (range 1–18) lines of therapy; 149 in a 2006–2010 cohort and 154 in a 2011–2016...
Dwight D. Eplin, Anna D. Jackson, Austin M. Smith, Brent Salvig, Wichai Chinratanalab, Bipin N. Savani
Pages: 229 - 233
The biologic medication filgrastim is approved by the Food and Drug Administration (FDA) to mobilize hematopoietic progenitor cells (HPCs) for collection by leukapheresis for autologous hematopoietic stem cell transplant (HSCT). The FDA-approved biologic tbo-filgrastim is currently used off-label for...