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Propose a Topic for New ASH Guidelines

On a continuous basis, ASH accepts proposals for new clinical practice guidelines. On an annual basis, proposals are reviewed by the ASH Committee on Quality. When prioritizing topics, the committee considers the following:

  • Is the proposed guideline topic important for hematologists (e.g., because of disease prevalence, impact of the disease on patients, high resource use or other factors)?
  • Would guidelines on the proposed topic address uncertainty regarding optimal practice or address unexplained variation in clinical practice?
  • Would guidelines address an underserved population or under-recognized health problem, i.e., potentially change clinical practice in ways that would improve health equity?
  • Is there published evidence to inform guidelines?
  • Is the topic not adequately addressed by existing guidelines?
  • Would guidelines on the topic align with other ASH strategic priorities and initiatives?

ASH members may submit proposals using the ASH Guideline Proposal Form. Non-ASH members may collaborate with an ASH member to submit a proposal. Completed forms should be submitted to [email protected].

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Prioritization Schedule

 Month(s) Overview
 June-September Call to ASH members for new proposals, when considered needed 
October-November  Review by Committee on Quality
December-April Project planning and budgeting   
 May Executive approval of plan and budget

Sample Guideline Topic Proposals

Please view two examples of successful guideline topic proposals below:

Previously Submitted

Each year, authors of previous submissions are invited to update and resubmit their previous proposal.

Submitted 9/7/2016

The American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism are a substantive body of work that offer a major contribution to clinician’s decision making about when to treat children with VTE.

However, these guidelines do not help the clinician in terms of which drug to use and how to use those drugs in children? What dosing? monitoring strategies? what are the effectiveness and side effect profiles of the various alternatives? how to transition from one drug to another depending on patient circumstances and duration of therapy?

Given that the bulk of children with thrombosis are either treated by pediatricians without specific hematology training, or adult hematologists without specific pediatric training, these issues are often poorly managed, and clinicians of all types are desperate for guidance.

Addressing the questions outlined in appendix 1, using the methodology established during 2018 guideline process would create the most useful guidelines to be viewed in conjunction with 2018 document to further support the ASH membership and broader global community in best practice management of neonates and children with VTE.

*Corresponding author: Paul Monagle, MD, BS, MSc, FRACP, FRCPA, MB
Institution: Victorian Children's Clinic

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 Submitted 4/1/2019

Thrombotic Thrombocytopenic Purpura (TTP) is an acute, life-threatening disorder caused by an acquired or congenital deficiency of ADAMTS13 and characterized by microangiopathic hemolytic anemia, profound peripheral thrombocytopenia, and organ ischemia. The purpose of this clinical practice guideline would be to outline best practices for diagnosis and treatment of TTP. This would update the 2012 guidelines from the British Committee for Standards in Hematology and would address the following questions:

  1. Diagnosis and evaluation
    a. What are the key clinical features of acquired and congenital TTP?
    b. What is the role of clinical prediction rules such as the French score or PLASMIC score in the diagnosis of TTP?
    c. How should laboratory assays (ADAMTS13 activity, antibodies, and inhibitors) be used in the diagnosis of TTP?
  2.  Management of acute TTP
    a. What is the ideal management of acute ITP?
    b. What is the role of rituximab in acute TTP (upfront therapy and refractory/relapsed TTP)?
    c. How should caplacizumab be used for acute TTP?
    d. How should refractory TTP be managed?
    e. What considerations are made for management of TTP in pregnancy?
  3. Management of TTP in remission
    a. How frequently should patients be monitored after recovery from acute TTP?
    b. How frequently should ADAMTS13 activity be monitored?
    c. Which patients, if any, should be offered pre-emptive rituximab to prevent relapse?
  4. Other
    a. What are the long-term sequelae and psychosocial implications of TTP?
    b. What are the cost implications of various TTP treatment strategies from a payor, patient, and healthcare system perspective?

*Corresponding author: Shruti Chaturvedi, MBBS, MS
Institution: The Johns Hopkins Hospital

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Submitted 9/7/2016

  • the current definitions for diagnosing the concerned entities (smoldering multiple myeloma, multiple myeloma, etc.,)
  • lay out the recommended choice of regimens, based on a given line of therapy (upfront, relapsed), keeping in mind the goals of treatment (transplant eligible, transplant ineligible) and specific comorbidities
  • role, and timing, of an auto transplant
  • role, and duration, of maintenance, along with the nature of agents to be used.
  • specific areas/interventions being looked at/studied/developed, which in turn might be what we might know to look out for in the near future

*Corresponding author: Philip Kuriakose, MD
Institution: Henry Ford Health System

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Submitted 9/16/2016

Chronic Lymphocytic Leukemia, monoclonal B cell lymphocytosis, and small cell lymphocytic lymphoma represent about 3% of my practice’s outpatient and new patient visits. OCM practices received data a few days ago on distribution of Medicare beneficiaries. In our practice chronic leukemia represented 3.3% of our beneficiaries, while nationwide it was slightly lower at 2.7%. A community hematologist who sees about 100 patients per week will see 3 or 4 of these patients per week. As a given patient will have more than one visit per year, most hematologists will have at least one or two per day. Guidelines generally recommend observation until symptomatic, and then provide pick list of treatments. In actuality, the decision is much more subtle. There are numerous choices each with different side effect profiles, thus, providing the opportunity for excess variation in treatment choices. Between 10 and 15% of these patients develop complications such as AIHA, ITP, opportunistic infections, or secondary malignancies, which are only briefly if at all addressed. All of these are complicated and difficult to evaluate and treat. Most of these patients live a long time, so age related comorbidity such as cardiac arrhythmias, anticoagulation, CKD, DM, obesity, and other malignancies, make evaluation and treatment much more complex. Last, new molecular testing is important for risk evaluation. Many payers do not cover some testing listed as “essential” such as IVGH or cytogenetics. It also not clear if patient’s benefit from some FDA approved therapies such as extended immunotherapy. In addition, since total cost data is now available from the OCM project, the cost of admissions, infections, cardiac and renal diseases can be considered. The opportunity to evaluate real total cost of care (Part A, Part B, Part D, lab, ED visits, admission, observation visits) provides a unique opportunity to address costly secondary events and look for opportunity to avoid those costs. Access to claims based data as well can identify how many patients have vaccines updated and how many get immunoglobulin support.

*Corresponding author: Paul Fishkin, MD
Institution: Illinois Cancer Care

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Submitted 1/28/2019

No abstract.

*Corresponding author: Steven L. Allen, MD
Institution: Northwell Health

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Submitted 9/12/2016

MM is the second most common adult hematologic malignancy. Despite numerous victories in drug discovery, most patients inevitably relapse, even after complete remission. In the up-front setting, the use of proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs) have been well-established over the past 10 years. High dose chemotherapy and autologous transplant has also maintained its status as an effective consolidative treatment (Palumbo et al, NEJM 2014; Attal et al, ASH 2015, abs 391; Cavo et al, ASCO 2016; abs 8000). More recently, post-transplant maintenance has been added to this regime with clear demonstration of benefit for progression-free survival (PFS) and even overall survival (McCarthy et al, NEJM 2012, Attal et al, ASCO 2016 abs 8001). With this powerful approach to therapy there has indeed been an improvement in survival. However, practitioners are now faced with a new question: what to do with these patients upon relapse. Finding the answer to this question is made more difficult by the pace of drug development in the relapsed setting and the upfront use of combination PI and IMiD therapy. With 5 new FDA-approved agents over the last 2 years, the ideal salvage regimen after an aggressive induction regime is not a clear choice. We thus propose to present an evidence-based approach to guide oncologists on which salvage therapies will best serve their patients in this particular setting.

*Corresponding author: Nina Shah, MD
Institution: UCSF Helen Diller Family Comprehensive Cancer Center

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Submitted 4/13/2020

Iron overload is the most important cause of morbidity and mortality in patients with thalassemia. Both patients with transfusion dependent thalassemia (TDT) and those with non-transfusion dependent thalassemia (NTDT) are at increased risk of iron overload, as a result of either frequent red blood cell transfusions or increased gastrointestinal absorption of iron. Iron accumulation is toxic to many tissues, causing heart failure, cirrhosis and fibrosis of the liver, renal dysfunction, solid and hematologic malignancies and growth retardation and multiple endocrine abnormalities.

Therefore, iron chelation is crucial in the management of patients with thalassemia to prevent such complications. Today, the goal of iron chelation therapy is to maintain safe levels of body iron at all times. Appropriate tailoring of iron chelation therapy with chelator choices and dose adjustment must be implemented in a timely manner. Similarly, adherence to long-term iron chelation therapy is crucial in preventing iron overload-related complications.

In recent years, there have been significant developments in the assessment of tissue iron overload, including the use of MRI for measuring liver and cardiac iron. In addition, treatment options have expanded, with the advent of oral iron chelators including oral deferiprone as tablet or solution form, and deferasirox in the form of dispersible tablet and more recently as film coated tablet, in addition to parenteral desferrioxamine.

However, the chelators differ strikingly in side-effect profile, cost, tolerability and ease of adherence, and efficacy for any specific patient. Careful dose adjustment is necessary to avoid excess chelation as iron levels fall. Another major challenge in chelation therapy is to achieve regular adherence to treatment regimens throughout a lifetime, as even unplanned periods of interruption to treatment can have damaging effects. Other disadvantages of iron chelation therapy include frequent side effects that require regular monitoring and a demanding regimen of parenteral formulation.

Many societies have developed recommendation statements based on expert consensus. However, there is a need to develop evidence-based recommendations that build on research advances seen in the last decade. Also, those recommendation need to consider contextual factors in order to help hematologist across the world understand the applications and limitations of iron chelators in various settings for thalassemia patients, and to point out areas for much-needed future research. This highlights the benefit of developing guidelines on iron chelation in this group of patients following the now highly regarded ASH guideline development process.

*Corresponding author: Ali Taher, MD, PhD, FRCP
Institution: American University of Beirut Medical Center

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Submitted 3/29/2019

Since the incidence of hematologic malignancies increases with age, there is a need to assess frailty in older adults with blood cancers. The age by itself must not be the unique factor in the treatment decision making process. Based on the previous work done by Klepin HD and Abel GA (1), we must define new concepts to be incorporated in our daily clinical practice such as frailty and adapted therapy based not only in comorbidities but also in functional decline associated to ageing. Practice patterns vary greatly in management of older patients in part due to lack of training on standardized approaches to assess fitness, vulnerability, or frailty in the context of treatment decisions. This can lead to potentially avoidable outcomes including excess toxicity or “under-treatment” due to assumptions made based chronologic age alone.

Last year, ASCO published guidelines for the Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy, with no commentaries on drugs only used in the treatment of patients with hematological malignancies (2).

Since the topic of geriatric hematology is too broad, in the proposed guideline we will focus only in the geriatric assessment/frailty screening recommendations for older patients with hematologic malignancies, highlighting the tools already validated in blood cancers. Following the practical assessment and management recommendations, we will propose elements to implement a geriatric hematology program based on local resources.

  1. Abel GA, Klepin HD. Frailty and the management of hematologic malignancies. Blood. 2018 Feb 1;131(5):515-524.
  2. Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, Canin B, Cohen HJ, Holmes HM, Hopkins JO, Janelsins MC, Khorana AA, Klepin HD, Lichtman SM, Mustian KM, Tew WP, Hurria A. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. J Clin Oncol. 2018 Aug 1;36(22):2326-2347.

*Corresponding author: Raul Cordoba, MD, PhD
Institution: University Hospital Fundacion Jimenez Diaz Avenida Reyes Catolicos

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Submitted 3/30/2019

Hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS) and hemophagocytic syndrome (HS) are often used interchangeably. In practice, secondary cases are by far more frequent. The genetic basis of inherited HLH forms are quite well studied and understood. Histiocyte Society criteria has been used widespread by Hematologists including secondary cases and useful as a good standard in establishing HLH diagnosis. However, strictly following the recommended criteria may lead to under diagnosis of secondary HLH cases. Sometimes, underlying conditions may hinder secondary HS diagnosis. I would like to give a few examples some of which are from my own experience. A post-chemotherapy AML patient with fever would be pancytopenic secondary to chemotherapy fulfilling one criteria that is not due to hemophagocytic process; might have high triglycerides secondary to TPN use and could not have any hemophagocytosis in the bone marrow due aplasia following chemotherapy. Thus, assessment of three of the eight criteria by HS have been complicated in such a patient. In a X-linked SCID due to IL-2 receptor gamma chain gene defect with HS, soluble IL-2 receptor levels were not elevated and there was no lymphocytosis. We had a T cell lymphoma patient who had HS without fever. There is a need for diagnostic criteria and treatment guidelines (when to start, which drug use algorithm to follow and how to monitor) for secondary HS. By establishing diagnostic criteria for secondary HS with flexibility to existing widely used criteria and therapeutic guidelines would help timely recognition and treatment of HS cases.

*Corresponding author: Sureyya Savasan, MD
Institution: Wayne State University

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Submitted 1/7/2019

Patients with hematologic malignancies and chronic non-malignant hematologic disorders such as sickle cell anemia and hemophilia suffer significant physical and psychosocial complications related to their disease and the intensive treatments, they require to achieve remission and potential cure. Advances in therapy have allowed patients to survive and turn their disease into a chronic illness, often requiring lifelong therapy that can be associated with significant side effects. In contrast to patients with solid tumors, patients with hematologic malignancies experience higher rates of hospitalization, more frequent admissions to the ICU, more in-hospital deaths and lower rates of referral to hospice with shorter stays in hospice.

Furthermore, specialty palliative care services are infrequently utilized in the management of patients with hematologic disorders. A number of barriers to the integration of palliative care and excellent end of life care have been identified, including policies by hospice agencies that do not allow transfusion support because of cost and logistics.

We propose to develop guidelines for the palliative care of appropriate patients with hematologic malignancy and chronic non-malignant disorders similar to the ASCO guidelines on the integration of palliative care into standard oncology care.1 We aim to address the following questions: 1) What is the optimal timing for palliative care involvement in patients with hematologic conditions? 2) Which components of palliative care delivery, such as symptom management or advanced care planning, are important? 3) Which interventions at the end of life or in hospice settings, such as transfusions, are associated with benefit in patients with hematologic conditions?

  1. Ferrell BR, Temel JS, Temin S, et al: Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 35:96-112, 2017.

*Corresponding author: Mark R. Litzow, MD
Institution: Mayo Clinic

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Submitted 1/28/2019

No abstract.

*Corresponding author: Steven L. Allen, MD
Institution: Northwell Health

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Submitted 7/30/2020

High-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double hit/triple hit lymphomas) account for less than 10% of all diffuse large B-cell lymphomas and have a worse prognosis1. Rearrangement of MYC in double hit/triple hit lymphoma is thought to represent a secondary event in the pathogenesis of the disease in the setting of complex chromosomal alterations2. A recent retrospective study from the Lunenburg Lymphoma Biomarker Consortium showed that outcome in patients with DLBCL morphology and double (or triple) hit lymphoma is influenced by MYC translocation partner (IG vs non-IG). MYC translocation was associated with inferior progression free survival and overall survival only if with an IG partner3. This would represent only ~50% of patients currently classified as having double (or triple) hit lymphoma. There is no standard of care for patients with double hit/triple hit lymphomas but a subgroup analysis from a prospective study suggests inferior outcomes with the use of RCHOP4. Most clinicians use more intense chemotherapy regimens like DA-R-EPOCH but these regimens are often times too toxic for elderly patients who are commonly affected by the disease.

Moreover, MYC and BCL2 protein coexpression occurs in 30% of patients and also leads to inferior survival5. Currently these patients are treated with RCHOP but there are ongoing clinical trials assessing new therapies.

Proposed guidelines would address appropriate molecular testing for these subgroups of patients and provide recommendations for induction and consolidation chemotherapy for patients of different age groups based on the current available evidence.


  1. Habermann, T. M., Macon, W. R., Maurer, M. J., Ketterling, R. P., Kurtin, P. J., Feldman, A. L., Vaidya, R., Cerhan, J. R., Ansell, S., Porrata, L., Nowakowski, G. S., Witzig, T. E., & McPhail, E. D. (2016). Treatment and Clinical Outcomes of High Grade B-Cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements (Double Hit/Triple Hit Lymphomas). Blood, 128(22), 155.
  2. Lindsley, R. C., & LaCasce, A. S. (2012). Biology of double-hit B-cell lymphomas. Current opinion in hematology, 19(4), 299-304.
  3. Sehn, L. (2019). Prognostic Significance of MYC Single, Double, Triple Hit and MYC-Translocation Partner Status in Diffuse Large B-Cell Lymphoma - a Study By the Lunenburg Lymphoma Biomarker Consortium (LLBC). [online] Ash.confex.com. Available at: https://ash.confex.com/ash/2018/webprogram/Paper113368.
  4. Green, T., Young, K., Visco, C., Xu-Monette, Z., Orazi, A., & Go, R. et al. (2012). Immunohistochemical Double-Hit Score Is a Strong Predictor of Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. Journal Of Clinical Oncology, 30(28), 3460-3467.
  5. Hu, S., Xu-Monette, Z., Tzankov, A., Green, T., Wu, L., & Balasubramanyam, A. et al. (2013). MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood, 121(20), pp.4021-4031.

*Corresponding author: Sami Ibrahimi, MD
Institution: University of Oklahoma Health Sciences Center

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Submitted 7/31/2020

There are many questions in the management of aplastic anemia (AA) that are not addressed by current guidelines. In speaking to physicians worldwide, the issues are, for the most part, repetitive, some of which are pointed out below (point #17). In current guidelines, many points are not included contributing to the uncertainty. Of course, some of the answers are scattered throughout the literature and in some cases, there is not a consensus or sufficient level of evidence to make a recommendation more strongly regarding management. But this is not spelled out, which could be helpful for treating physicians. In this scenario, acceptable possibilities given the best evidence will be beneficial rather than expect physicians to review the literature for many of these unanswered points.

The management of AA touches on almost every aspect of Hematology such as transfusions, infections, transplant, immunosuppressive therapy, testing for genetic defects, etc. The proposal for this guideline will be comprehensive and address several of the questions facing the hematologist in daily practice. When there is insufficient evidence to make a specific recommendation, this will be mentioned in the guideline. Also, it would be important to include physicians from different parts of the world since there are regional differences in management and this guideline could be more representative and inclusive. I am not sure if this is contemplated in this ASH initiative, but of course the plan can be adjusted to fit these goals and serve as a reference for the management of AA.

*Corresponding author: Phillip Scheinberg, MD
Institution: Hospital Sao Jose, Beneficencia Portuguesa de Sao Paolo

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Submitted 3/26/2019

Pregnancy is emerging as a life-threatening problem in SCD women, with higher rates of both pregnancy-related and SCD-related complications. Our team conducted a meta-analysis comparing pregnant women with and without SCD in high and low-income countries. We reported an 11-fold and 4-fold odds of maternal and perinatal death in pregnant women with SCD in both high and low-income countries (Boafor et al. BJOG. 2015).

In Ghana, SCD newborns approximate 15,000 (2%) per year [~2,400 (USA); ~300 (UK)]. Our multidisciplinary SCOB clinic has the largest cohort of pregnant SCD women (~250 cases/year), with a positive impact in reducing both maternal and perinatal mortality by 90% and 60% respectively (Asare et al. AJH. 2017) and maintaining similar maternal and perinatal mortality ratios among pregnant women with and without SCD (Oppong et al. AJH. 2018). Despite reduced mortality, morbidity remains high. Optimal approach to systematically reduce morbidity and mortality and manage complications in this cohort, remains unknown.

Primary clinical questions to be addressed:

  1. What is the optimal approach to management of acute events (pain, acute chest syndrome, anemia and venous thromboembolism)?
  2. What thresholds exist for diagnosing and managing hypertensive disorders in pregnancy in this cohort?
  3. What risk factors for adverse maternal and perinatal outcomes are modifiable?

This proposal has the unique potential to improve care for pregnant SCD women not only in low and middle-income countries, where ~80% of SCD population live, but also for those in high-income countries where maternal mortality is low, but pregnancy-related complications remain high.

*Corresponding author: Eugenia Vicky Naa Kwarley Asare, BSc
Institution: Ghana Institute of Clinical Genetics

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Submitted 4/2/2019

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Unites States with an annual incidence of around 20,000 and prevalence of around 150,000.1,2 In the last few years, the treatment paradigm for CLL has moved rapidly from the use of chemoimmunotherapy (CIT) such as FCR to the use of oral targeted therapies such as ibrutinib, venetoclax, idelalisib, and duvelisib. Given this dramatic change in treatment scenario, there is an emerging debate how best to incorporate these targeted therapies for our patients with CLL. Clinicians and patients are asking questions such as:

  1. Should CIT be abandoned for patients for CLL completely or be reserved for a selected group of patients and if yes, which patients?
  2. How do we choose amongst several approved targeted therapies; for e.g. both ibrutinib and the combination of venetoclax and rituximab are approved for R/R CLL – which therapy should we choose and why?
  3. What is the optimal sequence of novel therapies for an individual patient? Should patients receive a BTK inhibitor first and then a BCL2 inhibitor at progression, or vice versa?
  4. What is the role of cellular therapy in the current era?

These and many other questions are very pertinent to the field of CLL and will become even more important as many other targeted therapies (such as second generation BTK inhibitors, novel PI3K inhibitors) are in Phase III clinical trials in CLL and are expected to be approved over the course of next 1-2 years.3

*Corresponding author: Nitin Jain, MD
Institution: The University of Texas MD Anderson Cancer Center

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Submitted 9/12/2016

Would encompass all risk strata, elements of supportive care, including blood product support, and allogeneic transplantation.

*Corresponding author: Andrew Brunner, MD
Institution: Peter MacCallum Cancer Centre

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Submitted 9/12/2016

Multiple recent studies (Walter et al, Leukemia 2016, Walter et al, JCO 205, Sandmaier et al, Leukemia 2015 and Grimwade et al, NEJM 2016) have shown that the presence of minimal residual disease in AML strongly influences survival / relapse outcomes. Some of the studies also show while pre-transplant MRD predicts relapse and survival, post-transplant MRD negativity seems to have no major impact in high risk patients (Walter et al, Leukemia 2016). Many larger academic centers are now routinely testing MRD in AML patients both after chemotherapy, and in the pre- and post-transplant setting. However, there are currently no guidelines regarding the use of MRD testing in AML. It is an evolving field but I strongly feel guidelines based on the published literature will help clinicians properly use this very important prognostication tool.

*Corresponding author: Rizwan Romee
Institution: Washington University in St. Louis

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Submitted 5/30/2016

Myelodysplastic syndromes represent a diverse spectrum of malignancies arising from hematopoietic progenitors and generally presenting with bone marrow failure. Some patients will have more indolent disease, and die of other conditions, while others will have more aggressive disease and short survival. Many patients, however, fall into intermediate risk disease, and there is significant variation in the initiation of therapy, assessment of response, and decisions to change or alter therapeutic strategies. A guideline proposal would be to provide guidance for the a) initiation of azanucleosides (HMAs) in patients with MDS, b) monitoring of patients on HMA including dosing and dose delays, and c) determination of response and progression on treatment.

*Corresponding author: John Seymour, MBBS, PhD, FRACP
Institution: Massachusetts General Hospital

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Submitted 9/12/2016

Primary Clinical Question:

Does CML guidelines for adults need to be modified for pediatric patients?


Since tyrosine kinase inhibitors (TKI) (e.g. imatinib) emerged about 15 years ago, treatment of CML changed dramatically. Hematopoietic stem cell transplantation was the only curative measure before the era, but the current practice is to continue TKI indefinitely while role of stopping TKI in patients with deep molecular remission has been investigated in clinical trials. Because of less experience with CML in pediatric oncologists than adult oncologists, some pediatric patients with CML are followed by adult oncologists. There are a few guidelines for adult patients (guidelines from NCCN1 and ELN2). Because there are no guidelines specific for children and adolescents, the adult guidelines are often used. However, there are various issues that need to be considered because of different host factors in children who may need TKI for several decades. For instance, it is well known TKIs cause significant growth delay and careful monitoring is crucial.3 Existing prognostic scores (e.g. Sokal score) cannot be applied to children.4 Guidelines specific to pediatric patients will give valuable guidance to clinicians.

*Corresponding author: Sherif M. Badawy, MD, MS, MBBCh
Institution: Lurie Children's Hospital of Chicago | Pediatric Medicine

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Submitted 9/12/2016

Alloimmunization is a major clinical concern for patients who receive frequent blood transfusions from random donors. Alloantibodies which are directed against the class I human leucocyte antigens (HLA) on the platelet surface are associated with accelerated platelet destruction and eventual transfusion failure. The patient population affected by this disorder is heterogeneous including a wide variety of patients with both benign and malignant bone marrow failure disorders such as hypoproliferative myelodysplastic syndrome (MDS), acute leukemia, aplastic anemia, chemotherapy related bone marrow suppression and post-allogeneic transplant patients. In fact, approximately 17% of patients with AML receiving leucoreduced, single-donor, apheresis platelets became alloimmunized in the course of induction therapy1. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. Current practice includes the use of either cross matched platelets or HLA matched platelets when a patient is deemed platelet refractory. The choice of which modality is used depends on the accessibility by individual blood bank services and the superiority of one product over the other is not defined. The correct platelet threshold and indications when to prophylactically transfuse clinically stable, highly alloimmunized patients is also not known and therefore great heterogeneity exits among institutional practice. Aggressive, costly and often harmful recurrent transfusions to meet the generally accepted >10 000/μl threshold platelet count could be prevented with treatment algorithms and quality improvement initiatives in this very unique patient population.

*Corresponding author: Jennifer N. Saultz, DO
Institution: Oregon Health & Science University

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Submitted 4/24/2016

In myeloma genetic testing via FISH (and now other genetic tools) is considered standard of care. The information gleaned is of paramount importance in the clinic as it will guide patient and prognosis counseling and will assist in the selection of optimal therapies. While many studies are published a simple guide can be found in the Mayo Clinic recommendations for the management of myeloma patients. This treatment guideline has as its first step the identification of genetic subtype of the disease. Based on this genetic classification treatment pathways are recommended. For instance, patients with very high risk may need to start treatment with KRD and go to stem cell transplant (SCT). Patients with intermediate risk should receive initial treatment with VRD and then SCT. Patients with hyperdiploidy only can be offered treated with lenalidomide and dexamethasone alone and SCT can be deferred. The prognostic discussion is not the same for all; for myeloma cases with high-risk markers myeloma is not a “chronic disease.” Furthermore, treatment after SCT also varies by genetic category. Intermediate risk and higher should receive proteasome inhibitors such as bortezomib after SCT. In short, this knowledge greatly dictates clinical practice. What is the problem?

Myeloma patients are now routinely treated by the community doctors who refer patients after having started therapy. Oftentimes the first bone marrow sample was not properly tested for genetic markers. Most commonly FISH is done in unselected cells and thus the accuracy of the test is greatly diminished. By the time patients are seen by the transplant center the number of plasma cells in the bone marrow (due to the therapy given) is usually minimal such that extracting genetic information is nearly impossible. This needs to corrected.

*Corresponding author: Rafael Fonseca, MD
Institution: Mayo Clinic

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Submitted 9/12/2016

Primary clinical question:

In children and adolescents (age <18 years old) with acute myeloid leukemia and neutropenia, does the use of oral or intravenous prophylactic antibiotics and/or antifungals reduce infectious complications and related-mortality, compared to no antibiotic and/or antifungal prophylaxis?


Children and adolescents with acute myeloid leukemia (AML) receive intensive chemotherapy and at higher risk for prolonged neutropenia, infections, and associated mortality, when compared to other cancer diagnoses. The use of prophylactic antibiotics and/or antifungals has been associated with the concerns of developing resistant organisms.1-3 In children, adolescents, and adults with AML, or other cancer diagnosis, with chemotherapy-induced neutropenia, earlier studies have shown benefits of using prophylactic antibiotics,4-9 antifungals,10-12 or both13 with improved patients outcomes, including reduced morbidity and mortality. However, to date, practice variations exist among pediatric oncologists,1,2,14 and the adoption of prophylactic antibiotics and/or antifungals in a more systematic way remain limited.1,3,15 ACCL0934 is an ongoing COG trial evaluating the efficacy of prophylaxis with levofloxacin in reducing infection and its related-mortality in children with AML, relapsed ALL, or undergoing stem cell transplant. Infectious Disease Society of America (IDSA) 2010 Antimicrobial Agents in Neutropenic Patients with Cancer guidelines recommend prophylaxis in high risk adult patients defined as inducing an absolute neutrophil count (ANC) <100/mcl for >7 days,16 based upon accumulating evidence from randomized clinical trials that showed significant benefit with prophylactic antibiotics in high risk adult patients with a hematologic malignancies or undergoing stem cell transplant, including 33% reduction in infectious mortality.8

*Corresponding author: Sherif M. Badawy, MD, MS, MBBCh
Institution: Lurie Children's Hospital of Chicago | Pediatric Medicine

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Submitted 9/12/2016

International collaborations have changed the survival and success of treatment for countless childhood diseases, including Hodgkin lymphoma. To enhance international collaborations for childhood, adolescent and young adult Hodgkin lymphoma, harmonization of staging evaluation and response criteria is needed.

A collaborative group was formed during the First International Symposium on Childhood, Adolescent and Young Adult Hodgkin Lymphoma (ISCAYAHL) 2011 in Arlington, VA (USA) and leaders from prominent pediatric collaborative groups began to work towards harmonization as they recognized a profound need to standardize both staging and response criteria to facilitate the interpretation and comparison of clinical studies worldwide. The two protocols COG AHOD1331 and the EuroNet-PHL-C2 were reviewed for areas in need of harmonization as they represent the current standpoints of the major groups that treat the majority of pediatric patients with HL.

Areas in need of harmonization are: independent nodal regions, staging evaluation criteria, response criteria and modalities used in staging and response evaluations.

This harmonization effort will provide a framework to expedite identification of effective therapies by allowing for better comparisons of cooperative group trials and aid in the approval process for new agents by regulatory agencies. While some consensus statements may ultimately be founded on expert opinion, all effort will be made to base most of the consensus on published data.

*Corresponding author: Kara M. Kelly, MD
Institution: Roswell Park Comprehensive Cancer Center

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Submitted 8/26/2016

The WHO classification of Tumours of Haematopoietic Tissues provides clear diagnostic criteria for “AML with myelodysplasia-related changes” (hereafter referred to as MDS-AML). The application of these criteria and treatment decisions for these patients are far less clear. Patients with MDS by definition have <20% marrow blasts and AML patients (excluding AML with certain recurrent genetic abnormalities) have ≥20% marrow blasts. Patients with preceding MDS may “convert” to MDS-AML when their blast burden exceeds 20%. Patients may also present with ≥20% marrow blasts and have features consistent with MDS; this allows the diagnosis of MDS-AML rather than MDS or AML alone. What is the true significance of this 20% blast threshold? What features do these MDS-AML patients share in common with either MDS or AML that can help guide management decisions?

The MDS-AML group represents a unique entity within myeloid neoplasms that require special treatment considerations. These guidelines present the data regarding response of MDS-AML to various induction strategies. Herein we review the considerations of treatment response in this disease to identify appropriate candidates for stem cell transplant. We also consider special populations including pediatric patients with MDS-AML, patients with marrow failure syndromes, and patients with prior exposure to chemotherapeutic agents (treatment-related myeloid neoplasms) whose clinical presentation otherwise mirrors that of MDS-AML.

*Corresponding author: Matthew A. Kutny, MD
Institution: The University of Alabama at Birmingham

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Submitted 7/20/2020

In the last 10 years, cellular therapy has undergone revolutionary change with the advent of targeted T cell therapy. 1-4 5-13 Previously untreatable patients with refractory acute lymphoblastic leukemia and diffuse large B cell lymphoma, and mantle cell lymphoma are achieving durable remissions with chimeric antigen receptor T cell therapy (CAR-T). 14-17 5 6 8 However, these successes often come with significant side effects. 18-20 Though manageable in most cases, cytokine release syndrome (CRS) and neurotoxicity (ICANS - Immune Effector Cell-Associated Neurotoxicity Syndrome) occur in as many as 90% and 65% of CAR-T recipients respectively. 18 21 22 In addition, CAR-T related hyperactivation of macrophages and histiocytes (HLH/MAS) disorders and proinflammatory cytokine syndromes have been rarely described but can be fulminant, requiring prompt management. 18 Further, response to CAR-T has been associated with development of CRS/ICAN-ICE toxicities, limiting enthusiasm for pre-emptive approaches.

As CAR-T trials expand to treat non-hematologic diseases, identification of common toxicities and guidance on management strategies of these toxicities will be critical, both to differentiate tumor specific toxicities from those attributed to CAR-T, and to educate non-hematologists on acute management strategies. In addition, current guidance resources are not enough to guide specific interventions with tociluzumab or siltuximab, therapy/glucocorticoid therapy, as well as agents beyond REMS therapy such as anakinra, ibrutinib, IVIG, etc.

Recent grading consensus allows for uniform capture of CRS/ICANS and rarer events related to CAR-T. 23 24 However, this grading consensus does not provide direction on treatment and interventions associated with each grade. We believe that guidelines for diagnostic standards of evaluation for commonly encountered toxicities are needed to guide practitioners when common toxicities are encountered. While these guidelines are not meant to contradict the Risk Evaluation and Mitigation Strategies (REMS) developed by the FDA for the two CAR-T products (axicabtagene, ciloleucel, tisagenlecleucel, and brexucabtagene autoleucel) , they are meant to consolidate the companies’ toxicity management recommendations (which currently differ by the product) into one space and expand the guidance beyond what has been provided by REMS. Recent accumulation of experience and data exists for development of this timely guideline.

To that end, we propose that ASH consider developing a guideline on the management of both acute toxicities (i.e. CRS and ICANS25), and late toxicities26 (i.e., prolonged cytopenia, and on target off-tumor effects such as B-cell aplasia and hypogammaglobinemia seen with anti-CD19 CAR-Ts). Such guidelines will provide hematology practitioners, researchers, pharmacists, neurologist and critical care physicians an important resource needed to provide timely care that is uniform with the recent CAR-T toxicity grading. 27 28 23

As summarized in the table below, current CAR-T trials are available for CLL 29-33, ALL 34-37, DLBCL, NHL 38-39, Hodgkin 40, myeloma 41, sarcoma, gastric 42, pancreatic cancer 43, medullobastoma,44 ovarian cancer, neuroblastoma45, renal cell CA, breast cancer 46-49, mesothelioma, pancreatic50, lung 51-52, brain tumors. 53 Lessons learned from the methodology experience in recently produced guidelines in checkpoint inhibitors identify that development of these guidelines will help inform and identify CAR-T specific toxicities from tumor specific toxicity evaluations in the future. 45 54 Such a guideline should be based on expert opinions, published evidence and existing guidance.


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*Corresponding author: Jennifer Holter Chakrabarty, MD
Institution: University of Oklahoma Health Sciences Center

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