Rare Disease Report


Rare Diseases in Hematology

Rare hematological diseases fall into many subcategories, including anemia-type red blood cell conditions (eg, sickle cell disease, beta thalassemia, Diamond-Blackfan anemia), white blood cell dysfunctions associated with various malignancies (eg, follicular lymphoma, mantle cell lymphoma, chronic myeloid leukemia, hairy cell leukemia, multiple myeloma), immuno-disorders (eg, antiphospholipid syndrome, Evans syndrome, idiopathic neutropenia), platelet-based abnormalities that affect coagulation (eg, thrombotic thrombocytopenic purpura, Bernard-Soulier syndrome, Glanzmann’s thrombasthenia, gray platelet syndrome), and plasma-based issues (eg, hemophilia A and B, von Willebrand disease).

In addition, several other diseases, such as myeloproliferative disorders (eg, polycythemia vera, myelofibrosis, essential thrombocythemia, mastocytosis, eosinophilia), do not fit neatly into any of the above categories because multiple blood components are involved. Many inherited conditions that involve gene mutations (eg, Noonan syndrome, Imerslund-Grasbeck syndrome, prolidase deficiency, von Hippel-Lindau disease) defy easy classification as well, because blood problems are among multiple issues affecting different body systems.

Early Diagnosis Is Imperative

Some rare blood disorders—especially those that are gene-based— are easy to detect with a simple test, while others require substantial detective work to successfully diagnose. Due to the large number of blood conditions—common and uncommon—that are potential culprits, hematologists tend to be skilled investigators because they need to be experts in differential diagnosis.

The less time it takes to accurately diagnose a blood disorder, the better, because the patient may be suffering great pain; diagnosis and proper treatment can alleviate this.

  • Early diagnosis is often linked to improved treatment outcomes.
  • An established diagnosis means at-risk family members can be screened as soon as possible for the same condition.

Screening newborns for rare blood and other diseases is one way to further optimize diagnostic efficiency. This field, in particular, is marked by rapid technological advances; currently, about 4.1 million infants are screened annually for an ever-growing list of rare gene-based diseases.

Although the overwhelming majority of physicians, patient advocacy groups, and parents of children with genetic disorders are proponents of expanded screening, the practice is not without controversy: critics have raised issues related to cost-effectiveness, ethics, quality, and regulatory oversight.

Online Resources

Hematological diagnostic tests and procedures:
List of rare conditions:
Treatment guidelines:
FDA-approved orphan drugs:

Treatment Options

Treatment strategies for rare hematologic conditions are conditionspecific and widely vary. They include the addition and/or removal of blood components, growth-factor drugs, immunosuppressive drugs, stem cell and bone marrow transplantation, and gene-based medicine. If a condition is associated with either a benign tumor or a cancerous malignancy, biological agents or chemotherapy may be used.

Therapeutic efficacy varies widely. For many conditions—autoimmune hemolytic anemia, for instance—there are safe and effective treatments for managing or even curing the disease. Unfortunately, for many others, like sickle cell disease, there is a paucity or absence of viable treatment options. For the best outcome in any case, collaborative care that integrates all providers—from hematologist to pharmacist to surgeon to nurse—and caregivers is essential to optimal outcomes.

In the drug development field, orphan hematology is very active, and treatments for rare blood cancers are emerging particularly quickly.

Here is just a sampling of drugs the FDA has approved in the last 12 to 18 months:

  • Panobinostat (Farydak) and lenalidomide/dexamethasone (Revlimid/Decadron) for multiple myeloma (February 2015)
  • Ibrutinib (Imbruvica) for Waldenstrom’s macroglobulinemia (January 2015) and chronic lymphocytic leukemia (February 2014)
  • Blinatumomab (Blincyto) for acute lymphoblastic leukemia (December 2014)
  • Idelalisib (Zydelig) for chronic lymphocytic leukemia, non- Hodgkin lymphoma, and small lymphocytic lymphoma (July 2014)
  • Belinostat (Beleodaq) for peripheral T-cell lymphoma (July 2014) Treatments approved for other rare blood disorders during the same time period include:
  • Antihemophilic factor (recombinant), porcine sequence (Obizur) (October 2014), and antihemophilic factor (recombinant) and Fc fusion protein (Eloctate) (June 2014) for hemophilia
  • Siltuximab (Sylvant) for Castleman’s disease (April 2014)
  • Coagulation factor IX (recombinant) and Fc fusion protein (Alprolix) for hemophilia B (March 2014)

Some therapies that have been on the market longer include:

  • Prothrombin complex concentrate (Kcentra) for acquired hypoprothrombinemia
  • Hemin injection (Panhematin) for acute intermittent porphyria
  • Bosulif (Bosutinib), dasatinib (Sprycel), imatinib (Gleevec), interferon alfa-2a (Roferon-A), nilotinib (Tasigna), omacetaxine mepesuccinate (Synribo), and ponatinib (Iclusig) [Note: Ariad is the drug company, not the drug] for chronic myeloid leukemia
  • Antihemophilic factor (Alphanate), desmopressin acetate (Stimate), and coagulation factor VIII (Wilate) for von Willebrand disease

Ongoing Clinical Trials: An Overflowing Pipeline

Expansive research in genetics and molecular biology is resulting in enhanced understanding of hematological disease, identification of potential therapeutic targets that address disease on a molecular level, and development of novel treatments. Hundreds of late-stage clinical trials are in progress with hundreds of agents being evaluated to treat myriad manifestations of rare blood disease. A few of the treatment candidates now in phase 3 testing include:

  • Bortezomib/sorafenib, etoposide, and idarubicin: acute myelogenous leukemia
  • Cyclophosphamide/antithymocyte globulin: aplastic anemia
  • Ibrutinib, duvelisib, and ofatumumab: chronic lymphocytic leukemia and small lymphocytic lymphoma
  • Eculizumab: hemoglobinuria
  • Recombinant coagulation Factor VIIa, nonacog beta pegol: hemophilia A and B
  • Methylprednisolone/immunoglobulin: immune thrombocytopenic purpura
  • Oprozomib, pomalidomide, carfilzomib/dexamethasone, and bortezomib/dexamethasone: multiple myeloma
  • Poloxamer 188: sickle cell disease

Advocacy Support and Information

The rare-disease advocacy groups below provide resources and support for patients, caregivers, and clinicians. Appendix B of this resource guide includes a more comprehensive list:

Aplastic Anemia & MDS International Foundation, Inc:

American Society of Hematology:

Hemophilia Federation of America:

International Myeloma Foundation:

National Hemophilia Foundation:

Platelet Disorder Support Association:
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