Langerhans Cell Histiocytosis Treatment (PDQ®) 3/7 —Health Professional Version - National Cancer Institute

Langerhans Cell Histiocytosis Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Langerhans Cell Histiocytosis Treatment (PDQ®)–Health Professional Version

Treatment of Childhood LCH

In This Section

• Treatment of Low-Risk Single-System or Multisystem Disease
  • Isolated skin involvement
  • Skeletal involvement
  • CNS disease
• Treatment of High-Risk Multisystem Disease
• Treatment Options for Childhood LCH No Longer Considered Effective
• Treatment Options Under Clinical Evaluation
  • Current Clinical Trials
• Assessment of Response to Treatment

Over many years, national and international study groups have defined risk groups for allocation of Langerhans cell histiocytosis (LCH) patients to risk-based therapy on the basis of mortality risk and risk of late effects of the disease.

Depending on the site and extent of disease, treatment of LCH may include observation alone (after biopsy or curettage), surgery, radiation therapy, or oral, topical, and intravenous medication. The recommended duration of therapy is 12 months for patients who require chemotherapy for single-system bone, skin, or lymph node involvement.

For patients with both high-risk and low-risk multisystem disease, the reactivation rate after 6 months of therapy was as high as 50% on the HISTSOC-LCH-I and HISTSOC-LCH-II trials.[1,2] Based on data from the German-Austrian-Dutch (Deutsche Arbeitsgemeinschaft für Leukaemieforschung und -therapie im Kindesalter [DAL]) group trials, which treated patients for 1 year and had fewer relapses (29%),[1,3] the HISTSOC-LCH-III trial was designed to administer 12 months of chemotherapy for all high-risk multisystem patients and to randomly assign low-risk multisystem patients to either 6 months or 12 months of therapy. In patients with low-risk or high-risk disease who received 12 months of therapy, the reactivation rate was significantly reduced to approximately 30%.[4]

The standard treatment for LCH is chosen on the basis of data from international trials with large numbers of patients. However, some patients may have LCH involving only the skin, mouth, pituitary gland, or other sites not studied in these international trials. In these cases, therapy recommendations are based on case series that lack the evidence-based strength of the trials.

Clinical trials organized by the Histiocyte Society have been accruing patients on childhood treatment studies since the 1980s. Information about centers enrolling patients on these trials can be found on the ClinicalTrials.gov website.

Treatment of Low-Risk Single-System or Multisystem Disease

Treatment options for patients with low-risk single-system or multisystem disease depend on the site of involvement and include the following:

• Isolated skin involvement.
• Skeletal involvement.
• CNS disease.

Isolated skin involvement

Treatment options for patients with asymptomatic isolated skin involvement include the following:

1. Observation. Observation is recommended for all pediatric patients with skin-only LCH. These patients need to have a complete staging evaluation because 41% of skin-only patients referred to one center had multisystem disease requiring treatment.[5]

Therapy is suggested only for patients with symptomatic disease, which includes extensive rashes, pain, ulceration, or bleeding. Careful clinical (but not radiologic) follow-up of young infants with skin-only LCH is suggested because progression to high-risk multisystem disease is possible. Young children with skin-only LCH should be monitored periodically for many years because 1 of 19 children and 1 of 25 children in two series developed late diabetes insipidus.[6,7]

For patients who require therapy, treatment options for symptomatic isolated skin lesions include the following:

1. Topical steroids. Medium- to high-potency steroids are effective, but recurrence after discontinuation is common.[8]
2. Oral methotrexate. Oral methotrexate (20 mg/m2) weekly for 6 to 12 months.[9]
3. Oral hydroxyurea. Oral hydroxyurea (20 mg/kg) daily for at least 12 months.[10]
4. Oral thalidomide. Oral thalidomide 50 mg to 200 mg nightly.[11] Oral thalidomide may be effective for both pediatric and adult patients.
5. Topical nitrogen mustard. Topical application of nitrogen mustard can be effective for cutaneous LCH that is resistant to oral therapies, but not for disease involving large areas of skin.[12,13]
6. Psoralen and long-wave ultraviolet A radiation (PUVA) or UVB. Psoralen and PUVA or UVB can be effective in skin LCH, but its use is limited by the potential for late skin cancers, especially in patients with light skin tones.[14,15]
7. Chemotherapy. Systemic chemotherapy may be used in severe and symptomatic cases.

Skeletal involvement

Single skull lesions of the frontal, parietal, or occipital regions, or single lesions of any other bone

Treatment options for patients with single skull lesions of the frontal, parietal, or occipital regions, or single lesions of any other bone, include the following:

1. Curettage. Curettage only is the recommended therapy, when possible, for isolated bone lesions; curettage plus injection of methylprednisolone may also be used. LCH bone lesions may not need complete excision because this may increase healing time and the risk of long-term complications. Complete excision of skull lesions, which may require grafting, is not necessary.
   Low-dose radiation therapy is effective, but its use is limited in pediatric patients to lesions that threaten organ function.[16,17]; [18][Level of evidence: 3iiiA]

Skull lesions in the mastoid, temporal, or orbital bones

The mastoid, temporal, and orbital bones are referred to as CNS-risk bones. Risk refers to the increased risk of progression to diabetes insipidus followed by brain involvement.

The purpose of treating patients with isolated skull lesions in the mastoid, temporal, or orbital bones is to decrease the chance of developing diabetes insipidus and other long-term problems.[19]

Treatment options for patients with skull lesions in the mastoid, temporal, or orbital bones include the following:

1. Chemotherapy. The current treatment for CNS-risk bones is 12 months of vinblastine/prednisone therapy, as per the HISTSOC-LCH-III (NCT00276757) study:[4,19]
   • Weekly vinblastine (6 mg/m2) for 7 weeks for good response.
   • Daily prednisone (40 mg/m2) for 4 weeks, then tapered over 2 weeks.
   • Afterward, prednisone is given for 5 days at 40 mg/m2 every 3 weeks with the vinblastine injections.
   There is some controversy about whether systemic therapy is required for the first presentation of unifocal bone LCH, even in the CNS-risk bones. Orbital and ear, nose, and throat surgeons have reported a series of patients with orbital or mastoid lesions who received only surgical curettage.[20] None of these patients developed diabetes insipidus. However, when comparing the incidence rates of diabetes insipidus in patients who received little or no chemotherapy (20%–50% incidence) with the incidence rates reported by the German-Austrian-Dutch group DAL-HX 83 trial (10% incidence in patients treated for LCH), it appears that the weight of evidence from the DAL-HX 83 trial supports chemotherapy treatment to prevent diabetes insipidus in patients with LCH of the mastoid, temporal, or orbital bones.[3,21] It should be noted, however, that the DAL-HX studies administered more drugs and treated patients for 12 months.

Vertebral or femoral bone lesions at risk of collapse

Treatment options for patients with vertebral or femoral bone lesions at risk of collapse include the following:

1. Observation. A single vertebral body lesion without soft tissue extension to the extradural space may be observed only.
2. Low-dose radiation therapy. Low-dose radiation therapy may be used to promote resolution in an isolated vertebral body lesion or a large femoral neck lesion at risk of fracture, where chemotherapy is not usually indicated (single bone lesion). Despite the low dose required (7–10 Gy), radiation therapy should be used with caution in the area of the thyroid gland, brain, or any growth plates.[22]
3. Chemotherapy. Patients with soft tissue extension from vertebral lesions are often treated successfully with chemotherapy,[23][Level of evidence: 3iiDiii] but prolonged therapy does not appear to be needed beyond the period required to reduce the mass and any risk to the spinal cord. The risk of reactivation of a single bone lesion was only 9% in one large retrospective series.[24]
4. Bracing or spinal fusion. When instability of the cervical vertebrae and/or neurologic symptoms are present, bracing—or rarely, spinal fusion—may be needed.[25] Patients with soft tissue extension from the vertebral lesions are often treated successfully with chemotherapy.[23][Level of evidence: 3iiDiii]

Multiple bone lesions (single-system multifocal bone lesions)

Treatment options for patients with multiple bone lesions (single-system multifocal bone lesions) at risk of collapse include the following:

1. Chemotherapy. The most commonly used systemic chemotherapy regimen is the combination of vinblastine and prednisone. Based on the results of the HISTSOC-LCH-III (NCT00276757) trial, 12 months of treatment with weekly vinblastine (6 mg/m2) for 7 weeks, then every 3 weeks, is used for good responders.[4] Prednisone (40 mg/m2) is given daily for 4 weeks, then tapered over 2 weeks. Afterward, prednisone is given for 5 days at 40 mg/m2 every 3 weeks with the vinblastine injections. A short treatment course (<6 months) with only a single agent (e.g., prednisone) is not sufficient, and the number of relapses is higher. A reactivation rate of 18% was reported with a multidrug treatment regimen that was used for 6 months versus a historical reactivation rate of 50% to 80% with surgery alone or with a single-drug treatment regimen.[26] A comparison of results from two Japanese trials revealed no improvement in progression-free survival (66% vs. 65%) when additional prednisone and a prolonged maintenance phase were added.[27]

(Refer to the Multiple bone lesions in combination with skin, lymph node, or diabetes insipidus [low-risk multisystem LCH] section of this summary for information about additional agents used to treat multifocal bone LCH.)

Multiple bone lesions in combination with skin, lymph node, or diabetes insipidus (low-risk multisystem LCH)

Treatment options for patients with multiple bone lesions in combination with skin, lymph node, or diabetes insipidus (low-risk multisystem LCH) include the following:

1. Chemotherapy (vinblastine and prednisone). Vinblastine and prednisone in combination. Based on the results of the randomized HISTSOC-LCH-III (NCT00276757)trial, the same chemotherapy regimen of vinblastine and prednisone, as described above, is used for 12 months. Patients without risk-organ involvement who were randomly assigned to receive 12 months of treatment with vinblastine/prednisone had a lower 5-year reactivation rate (37%) than did patients who received only 6 months of treatment (54%; P = .03) and patients treated with historical 6-month schedules (52% [HISTSOC-LCH-I] and 48% [HISTSOC-LCH-II]; P < .001). Most disease reactivations were in bone, skin, or other nonrisk locations.[4]
   Patients with low-risk multisystem LCH have a survival rate of almost 100%, but reactivations were shown to be major risk factors for significant late effects on the DAL and Histiocyte Society trials.[3,4]
2. Chemotherapy (other regimens). Other chemotherapy regimens have also been effective, including the following:
   • Vincristine, cytosine arabinoside, and prednisone in combination.[28] This combination has been proven to be an effective frontline or salvage therapy. However, prednisone is now given for a much shorter time than was originally published (52 weeks): 4 weeks at 40 mg/m2 then tapered to 20 mg/m2 by week 6 during the induction phase, and for 5 days every 3 weeks at 20 mg/m2 with a single dose of vincristine and 5 days of cytosine arabinoside during maintenance.
   • Cladribine. Cladribine given at 5 mg/m2 per day for 5 days every 3 weeks for two to six cycles can be an effective salvage therapy for recurrent bone or low-risk multisystem disease.[29] More than six cycles is not recommended because of the risk of cumulative cytopenias.
3. Bisphosphonate therapy. Bisphosphonate therapy can also be effective for treating LCH bone lesions.[30,31] A nationwide survey from Japan described 16 children treated with bisphosphonates for bone LCH. All of the children had bone disease; none had risk-organ disease. Most patients received six cycles of pamidronate at 1 mg/kg per course given at 4-week intervals. In 12 of 16 patients, all active lesions including skin (n = 3) and soft tissues (n = 3) resolved. Eight patients remained disease free at a median of 3.3 years.[32] Other bisphosphonates such as zoledronate have been used to successfully treat bone LCH.[33]
   Although bisphosphonates are used for bone LCH, some publications report response in other organs, such as skin.[31,32]

CNS disease

CNS lesions

The three types of LCH CNS lesions are as follows:

• Mass lesions or tumors in the cerebrum, cerebellum, or choroid plexus.
• Mass lesions of the hypothalamic-pituitary axis that are always associated with diabetes insipidus and are often associated with other endocrinopathies.
• Neurodegenerative syndrome. T2 fluid-attenuated inversion recovery (FLAIR) hyperintense signals are present, most often in the cerebellar white matter, pons, basal ganglia, and, sometimes, in the cerebrum.

Drugs that cross the blood-brain barrier, such as cladribine, or other nucleoside analogs, such as cytarabine, are used for active CNS LCH lesions.

Treatment options for patients with CNS lesions include the following:

1. Chemotherapy (cladribine). Treatment of mass lesions with cladribine has been effective in 13 reported cases.[34,35]; [36][Level of evidence: 3iiiDiii] Mass lesions included enlargement of the hypothalamic-pituitary axis, parenchymal mass lesions, and leptomeningeal involvement. Doses of cladribine ranged from 5 mg/m2 to 13 mg/m2, given at varying frequencies.[36][Level of evidence: 3iiiDiii]
2. Chemotherapy (other regimens). Patients with LCH and mass lesions in the hypothalamic-pituitary region, the choroid plexus, the grey matter, or the white matter may also respond to standard LCH chemotherapy.[37,38] Treatment with vinblastine with or without corticosteroids for patients with CNS mass lesions (20 patients; mainly pituitary) demonstrated an objective response in 15 patients; 5 of 20 patients achieved a complete response, and 10 of 20 patients achieved a partial response.

CNS neurodegenerative syndrome

There is no established optimal therapy for CNS neurodegenerative LCH, and assessment of response can be difficult.[39]

It is not clear whether LCH changes in the cerebellum, pons, and basal ganglia diagnosed by magnetic resonance imaging (MRI) and without clinical neurologic findings should be treated. Early studies suggested that not all LCH-related radiologic changes progressed to clinical neurodegenerative disease. However, treatment in the early stages of clinical disease before permanent damage occurs appears to be important. The current recommendation is ongoing neurologic evaluation both clinically and with MRI scanning; therapy is started as soon as clinical neurodegenerative disease progression is noted. It is unclear whether progressive radiologic changes should be an indication for treatment.[40] In this regard, studies of cerebrospinal fluid (CSF) and serum biomarkers in an attempt to predict and prevent neurodegenerative disease are ongoing.[39]

Drugs used in active LCH, such as dexamethasone and cladribine, along with other agents, such as all-trans retinoic acid (ATRA), intravenous immunoglobulin (IVIG), infliximab, and cytarabine with or without vincristine, have been used in small numbers of patients with mixed results. Many of these agents may result in the complete or partial resolution of radiographic findings, but definitive clinical response rates have not been rigorously defined.[40-44]; [36][Level of evidence: 3iiiDiii]

• ATRA. ATRA was given at a dose of 45 mg/m2 daily for 6 weeks, then 2 weeks per month for 1 year.[41] Patients were reported to have stable clinical status at 1 year.
• IVIG. IVIG (400 mg/m2) alone given monthly or in combination with chemotherapy has been reported to result in stabilization of disease and even transient improvements in some patients. The duration of therapy is undefined and may be prolonged or even lifelong.[39,45]
• Chemotherapy. A study using cytarabine with or without vincristine for up to 24 months reported improvement in the clinical and MRI findings in some patients and stabilization of disease in the others.[40][Level of evidence: 3iiiC] Seven of eight patients were monitored for more than 8 years after stopping therapy and had stable neurologic and radiographic findings.
  In the Japan LCH Study Group-96 Protocol, cytarabine failed to prevent the onset of neurodegenerative syndrome. Patients received cytarabine 100 mg/m2 daily on days 1 to 5 during induction and 150 mg/m2 on day 1 of each maintenance cycle (every 2 weeks for 6 months). Three of 91 patients developed neurodegenerative disease, which is similar to the rate reported for patients on the Histiocyte Society studies.[46]
• BRAF V600E inhibitor therapy. Very early results confirm the activity of BRAF V600E inhibitor therapy in BRAF V600E–positive LCH. The earliest published results included eight adults with BRAF-mutated Erdheim-Chester disease treated with vemurafenib; four patients also had LCH, and two of these patients had involvement of the cerebellum and pons. All patients had a good response to vemurafenib. One patient developed a cutaneous squamous cell carcinoma that was treated with surgical excision.[47] Three patients with neurodegenerative-disease LCH who had progressive disease 1 to 3 years after cytotoxic chemotherapy were treated with either vemurafenib or dabrafenib and had complete (n = 1) or partial (n = 2) clinical and radiologic responses. Another patient who had neurodegenerative-disease LCH for more than 10 years developed progressive disease but had limited exposure to these agents because of excessive cutaneous and joint toxicities.[48]

Early recognition of clinical neurodegeneration and early institution of therapy appear to be vital for success of therapy. Studies combining MRI findings together with CSF markers of demyelination, to identify patients who require therapy even before onset of clinical symptoms, are underway in several countries.

Treatment of High-Risk Multisystem Disease

Treatment options for patients with high-risk multisystem disease (spleen, liver, and bone marrow involving one or more sites) include the following:

1. Chemotherapy.

Evidence (chemotherapy):

1. In the HISTSOC-LCH-II and HISTSOC-LCH-III (NCT00276757) studies, the standard arm consisted of vinblastine and prednisone, as described above, but mercaptopurine was added to the continuation phase of the protocol.[3,19]
   • The standard therapy length recommended for LCH involving the spleen, liver, or bone marrow (high-risk organs) is now 12 months, based on the DAL-HX 83 and HISTSOC-LCH-III studies.
2. The HISTSOC-LCH-II study was a randomized trial to compare treatment of patients with either vinblastine, prednisone, and mercaptopurine or vinblastine, prednisone, mercaptopurine, and etoposide.[2][Level of evidence: 1iiA]
   • There was no statistically significant difference in outcomes (response at 6 weeks, 5-year probability of survival, relapses, and permanent consequences) between the two treatment groups. Hence, etoposide has not been used in subsequent Histiocyte Society trials.
   • Late review of the results, however, reported reduced mortality of patients with risk-organ involvement in the etoposide arm.[2]
3. Although controversial, a comparison of patients in the HISTSOC-LCH-I trial with patients in the HISTSOC-LCH-II trial suggested that increased treatment intensity promoted additional early responses and reduced mortality. It is important to note that those studies included lungs as risk organs. However, subsequent analyses have shown that lung involvement lacks prognostic significance.[49]
4. The HISTSOC-LCH-III (NCT00276757) study randomly assigned risk organ–affected patients to receive either vinblastine/prednisone/mercaptopurine or vinblastine/prednisone/mercaptopurine plus methotrexate (intravenous during the induction phase and oral in the continuation phase).[4]
   1. The response rates at 6 and 12 weeks and overall survival (OS) were not improved; however, there were significantly increased grade 3 and grade 4 toxicities in patients who received methotrexate.
   2. An important finding of the HISTSOC-LCH-III study was that the mortality of patients with high-risk LCH on both arms of the study was significantly reduced compared with that of patients on the earlier HISTSOC-LCH-II study, even though the standard arm utilized the same drugs. Possible explanations for reduced mortality include the following:
      • A second 6-week induction phase of weekly vinblastine with prednisone was administered for 3 days per week. This reinduction phase was given to all patients who did not achieve a status of no active disease by the end of the 6-week induction phase, before going onto the every-3-weeks maintenance courses. The rate of no active disease increased after the second induction phase; this course may have played a significant role in the reduced mortality rate.
      • Better supportive care.
      • Earlier change to an effective salvage strategy for nonresponsive lesions.
   3. It should be noted that although survival was improved in the HISTSOC-LCH-III study, only 60% of patients had no active disease in risk organs after a year of therapy, and 25% to 29% of patients relapsed.
5. The Japan LCH Study Group (JLSG) reported the following results for patients treated on the JLSG-96 trial. Treatment included a 6-week induction regimen of cytosine arabinoside, vincristine, and prednisolone followed by 6 months of maintenance therapy with cytarabine, vincristine, prednisolone, and low-dose intravenous methotrexate. If patients had a poor response to the initial regimen, they were switched to a salvage regimen of intensive combination doxorubicin, cyclophosphamide, methotrexate, vincristine, and prednisolone.[46]
   • The 5-year response rate was 78%, and the OS rate was 95% for patients with multisystem disease.
   • Diabetes insipidus occurred in 8.9% of patients with multisystem disease.
   • Similar to the HISTSOC-LCH-III (NCT00276757) study, the important finding of this study was the decreased mortality compared with previous JLSG studies and to the HISTSOC-LCH-II study. This was attributed to the early change to a more effective salvage therapy for patients with nonresponsive disease, as well as better supportive care.[46]
   • The study had a high reactivation rate, which prompted several changes, including an increase in the duration of the trial to 12 months and the addition of vinblastine, prednisone, mercaptopurine, and methotrexate.[50]
6. The JLSG-02 protocol was similar to the JLSG-96 study, except for adding cyclosporine to the reinduction of poor responders and increasing the length of treatment to 54 weeks for good responders and 60 weeks for poor responders.[51]
   • Despite a markedly increased intensity of treatment, the event-free survival (EFS) was only 46% for high-risk patients and 70% for low-risk patients, whereas the rates for the HISTSOC-LCH-III study were 70% and 63%.

Seventy-five percent of children with sclerosing cholangitis will not respond to chemotherapy because the LCH is no longer active, but the fibrosis and sclerosis remain. Despite the limitations, liver biopsy may be the only way to distinguish active LCH from end-stage fibrosis. Liver transplantation is the only alternate treatment when hepatic function worsens. In one series of 28 children undergoing liver transplantation, 78% survived and 29% had recurrence of LCH, but only two cases of recurrent LCH occurred in the transplanted liver, although other cases have been reported since publication of the initial data.[52] If possible, active LCH should be under control before transplantation. Patients who undergo liver transplant for LCH may have a higher incidence of posttransplant lymphoproliferative disease.[53]

Some patients develop a macrophage activation of their marrow. This may be confusing to clinicians, who may think the patient has hemophagocytic lymphohistiocytosis and LCH. The best therapy for this life-threatening manifestation is not clear because it tends not to respond well to standard hemophagocytic lymphohistiocytosis therapy. Clofarabine, anti-CD52 antibody alemtuzumab, or reduced-intensity allogeneic stem cell transplant could be considered.[54]

Treatment Options for Childhood LCH No Longer Considered Effective

Treatments that have been used in the past but are no longer recommended for pediatric patients with LCH in any location include cyclosporine [55] and interferon-alpha.[56] Extensive surgery is also not indicated. Curettage of a circumscribed skull lesion may be sufficient if the lesion is not in the temporal, mastoid, or orbital areas (CNS risk). Patients with disease in these particular sites are recommended to receive 6 months of systemic therapy with vinblastine and prednisone. For lesions of the mandible, extensive surgery may destroy any possibility of secondary tooth development. Surgical resection of groin or genital lesions is contraindicated because these lesions can be healed by chemotherapy.

Radiation therapy use in LCH has been significantly reduced in pediatric patients, and even low-dose radiation therapy should be limited to single-bone vertebral body lesions or other single-bone lesions compressing the spinal cord or optic nerve that do not respond to chemotherapy.[57]

Treatment Options Under Clinical Evaluation

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

The following are examples of national and/or institutional clinical trials that are currently being conducted:

• HISTSOC-LCH-IV (NCT02205762) (LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With LCH): On the basis of features at presentation and response to treatment, the LCH-IV study tailors treatment to one of the following seven strata:
  • Stratum I: First-line treatment for multisystem LCH patients (group 1) and patients with single-system LCH with multifocal bone or CNS-risk lesions (group 2).
  • Stratum II: Second-line treatment for nonrisk patients (patients without risk-organ involvement who fail first-line therapy or have a reactivation after completion of first-line therapy).
  • Stratum III: Salvage treatment for risk LCH (patients with dysfunction of risk organs who fail first-line therapy).
  • Stratum IV: Stem cell transplantation for risk LCH (patients with dysfunction of risk organs who fail first-line therapy).
  • Stratum V: Monitoring and treatment of isolated tumorous and neurodegenerative CNS LCH.
  • Stratum VI: Natural history and management of other single-system LCH (patients who do not need systemic therapy at the time of diagnosis).
  • Stratum VII (long-term follow up): All patients, regardless of previous therapy, will be monitored for reactivation or permanent consequences once complete disease resolution has been achieved and the respective protocol treatment has been completed.
• NCT02670707 (Vinblastine/Prednisone Versus Single Therapy With Cytarabine for LCH):The purpose of this trial is to compare previously used vinblastine/prednisone to single therapy with cytarabine for LCH.

It is preferable that patients with LCH be enrolled in a clinical trial whenever possible so that advances in therapy can be achieved more quickly, utilizing evidence-based recommendations and to ensure optimal care. Information about clinical trials for LCH in children is available from the NCI website, Histiocyte Society websiteExit Disclaimer and the North American Consortium for Histiocytosis (NACHO) websiteExit Disclaimer.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Assessment of Response to Treatment

Response assessment remains one of the most difficult areas in LCH therapy unless there is a specific area that can be followed clinically or with sonography, computed tomography (CT), or MRI scans, such as the skin, hepato/splenomegaly, and other mass lesions. Clinical judgment, including evaluation of pain and other symptoms, remains important.

Bone lesions may take many months to heal and are difficult to evaluate on plain radiographs, although sclerosis around the periphery of a bone lesion suggests healing. CT or MRI scans are useful in assessing response of a soft tissue mass associated with a bone lesion, but are not particularly helpful in assessing the response of lytic bone lesions. Technetium Tc 99m bone scans remain positive in healing bone. Positron emission tomography (PET) scans may be helpful in following the response to therapy because the intensity of the PET image diminishes with the response of lesions and healing of bone.[58]

For children or adults with lung LCH, pulmonary function testing and high-resolution CT scans are sensitive methods for detecting disease progression.[59] Residual interstitial changes reflecting residual fibrosis or residual inactive cysts must be distinguished from active disease; somatostatin analogue scintigraphy may be useful in this regard.[60]

References

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