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Lymphohistiocytosis (Hemophagocytic Lymphohistiocytosis) Follow-up

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
Updated: May 18, 2016

Further Outpatient Care

See the list below:

  • Supportive care is needed to ensure that the patient with hemophagocytic lymphohistiocytosis (HLH) remains stable until a bone marrow donor can be found. This includes transfusions of RBCs, platelets, and fresh frozen plasma, as well as nutritional support in addition to the treatment protocol. [38]
  • Patients should be continually monitored for evidence of infection because of their immunosuppressed state. Be aware of the possibility of underlying malignancy.
  • Biopsies and diagnostic cytogenetics may be needed in addition to selective radiographic imaging. [22]


See the list below:

  • Complications of individual drugs in the regimen were outlined above (see Medication).
  • Complications due to a subsequent transplant are numerous and include both acute and chronic graft versus host disease, acute inflammatory events, respiratory distress syndrome, and exacerbation of neurologic symptoms. [43]


Although the prognosis varies between studies and with different approaches to treatment, the disease is invariably fatal if not treated. The median survival rate has been reported to be 2-6 months without treatment, but survival time has dramatically improved with the advent of the HLH-94 protocol already discussed.

A study of 122 patients from the International Registry for hemophagocytic lymphohistiocytosis found that the overall estimated 5-year survival rate was 21%, with 66% of patients who received bone marrow transplantation (BMT) surviving 5 years versus only 10.1% of patients treated with chemotherapy alone.[24] More recent studies have shown that the HLH-94 protocol resulted in an overall survival rate of 55%. Success or failure of an allogeneic BMT is the most important long-term prognostic factor. Unfortunately, many cases are diagnosed late in the course of the disease, after irreversible damage has occurred.

Although patients with hemophagocytic lymphohistiocytosis are at high risk for death early in their disease course, steroids, intravenous immunoglobulin (IVIG), or both may be sufficient as first-line therapy for selected patients.[44]

The ratio of C16 –ceramide to sphingosine was elevated in those who died despite appropriate treatment, but remained low in survivors, implying that this ratio may be of prognostic significance.[45] The balance of ceramide and sphingosine may be pivotal in the clinical outcome for these patients.


Patient Education

See the list below:

  • All physicians who treat young patients must be aware of life-threatening diseases such as hemophagocytic lymphohistiocytosis.
  • Pediatricians, dermatologists, and neurologists should especially take note because the presenting symptoms of hemophagocytic lymphohistiocytosis are likely to bring the patient into their offices.
  • Any suspicion warrants a referral to a pediatric hematologic-oncologist who is equipped with the necessary tools to make a rapid diagnosis.
Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Kathleen M Sakamoto, MD, PhD Shelagh Galligan Professor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Nicole L Lacz, MD, and Franklin Desposito, MD, to the original writing and development of this article.

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A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.
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