Rare Classroom: Systemic Anaplastic Large Cell Lymphoma

Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about, or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Systemic Anaplastic Large Cell Lymphoma

Also known as primary systemic anaplastic large cell lymphoma.

What is Systemic Anaplastic Large Cell Lymphoma?

  • A rare type of T-cell lymphoma
  • Characterized by large cells that are different in size and shape.
  • Defined by the uniform expression of a special marker on the lymphoma cells called CD30
  • Aggressive, fast growing lymphomas
  • Usually derive from cytotoxic T-cells
  • Two groups – Anaplastic lymphoma kinase positive and negative:
    • ALK-positive
    • Responds well to standard chemotherapy treatments
    • ALK-negative
    • Initially respond to treatment, but more people will relapse within five years than those with ALK-positive ALCL
  • Typically diagnosed when in an advanced stage (III or IV) and rapidly progressive
  • Systemic anaplastic large cell lymphoma (sALCL) represents 2-8% of adult non-Hodgkin lymphoma cases and as many as 30% of childhood non-Hodgkin lymphoma cases
  • 60% of patients with ALCL are ALK+

How Do You Get It?

  • No decisive risk factors have been identified for this disease.
  • ALK+:
    • Genes overexpressed: BCL6, PTPN12, CEBPB, and SERPINA1
    • Predominantly affects children and young adults
    • More males than females
  • ALK-:
    • Genes overexpressed: CCR7, CNTFR, IL22, and IL21
    • 60-70% relapse within 5 years
    • Affects both genders equally
    • Occurs in older patients

What Are The Symptoms?

  • Common symptoms of this cancer include:
    • Weight loss
    • Night sweats
    • Fevers
    • Fatigue
    • Cough
    • Enlarged lymph nodes – most commonly in neck and arm pits
  • Common areas of involvement include:
    • Bone marrow (30 percent)
    • Skin (21 percent)
    • Bones (17 percent)
    • Soft tissue (17 percent)
    • Lungs (11 percent)
    • Liver (8 percent)
    • In rare cases, the central nervous system and digestive tract may be affected.

How Is It Treated?

  • The most common, first line treatment for systemic anaplastic large cell lymphoma is chemotherapy.
  • Chemotherapy approaches include:
    • The standard first line treatment is the chemotherapy regime CHOP
      • Cyclophosphamide (Cytoxan, Endoxan)
      • Adriamycin (hydroxy doxorubicin)
      • Vincristine (Oncovin)
      • Prednisone
    • Regimen is given every 21 days with Cytoxan, Adriamycin, and Vincristine given on the same day via infusion and prednisone taken daily by mouth for 5 days at the beginning of the cycle
    • Commonly CHOP is given for at least 6 cycles
    • CHOP with etoposide (CHOEP) is sometimes recommended to young patients with ALK+ ALCL
    • ALK+ typically has a positive response to CHOP regimes
    • ALK- has a less favorable response to CHOP
  • Radiation therapy may be employed in some cases following a course of chemotherapy.
    • Generally considered in areas with bulky disease (areas of large tumor or lymph nodes)
    • Lymph cells are very sensitive to radiation, making this an effective treatment in some cases 
  • High-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC/HSCT)  is used in relapsed/refractory patients
    • After induction chemotherapy with CHOP, patients with ALK− ALCL often receive a consolidative transplantation in first complete remission 
    • It is not currently clear which patients are best suited for this approach. More information is needed to select high-risk patients who may benefit. Ideally, treatment would incorporate clinical and genetic factors.
    • HDC and ASCT represent the standard of care for relapsed ALCL if chemo sensitivity is demonstrated
  • Brentuximab vedotin (Adcetris) is a CD30-specific antibody-drug conjugate used for relapsed/refractory patients
    • Approved in 2011 for use in systemic anaplastic large cell lymphoma (sALCL) after failure of at least 1 multi-agent chemotherapy regimen
    • Considered a standard of care for patients with relapsed or refractory sALCL
    • Both ALK-positive and ALK-negative subtypes of ALCL have been shown to respond well to brentuximab vedotin
  • Pralatrexate (Folotyn)
    • FDA approved in 2009 for relapsed/refractory peripheral T-cell lymphoma
    • Approval was based on the overall treatment response rate of patients in a clinical trial; however, clinical benefit such as progression- free survival or overall survival was not demonstrated
    • Folotyn (pralaterxate) is a folate analogue metabolic inhibitor that interferes with cellular metabolism
    • Limited information is available for the use of Folotyn specifically for sALCL
    • Approved for use in US, Australia and South Korea
  • Other potential treatments for this cancer include Romidepsin (Istodax) and Belinostat (Beleodaq)
  • Prognosis varies by type
    • Relapses occur but they are typically sensitive to chemotherapy
    • Systemic ALCL ALK+ 5-year survival: 70-80%
    • Systemic ALCL ALK- 5-year survival: 15-45%
  • Prognosis is also dependent on:
    • Age
    • LDH (lactate dehydrogenase) values
    • Performance status (describes the patient’s level of functioning)
    • Number of extranodal sites
    • Stage

Where Can I Learn More???

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