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Prognosis for non-Hodgkin's lymphoma

 

Prognosis for non-Hodgkin's lymphoma.

As you go through treatment, and read more about lymphoma you will hear a lot about the results of your treatment, or clinical trial results. The currently accepted method to evaluate the response to treatment is the Cheson criteria.

Click on any of the terms below to go to their definition.

International Prognostic Indexes

Cure

Where there are no signs of the disease reappearing, doctors may cautiously begin using the word cure. The ability to cure NHL depends on the type of lymphoma. Many high-grade lymphomas can be cured. Low-grade NHLs tend to reappear, even after long-term remission. The usual standard for aggressive lymphomas is that you must be in complete remission 5 years or more before they will consider calling you cured.

 

Complete remission: 

This term is used when all signs of the disease have completely disappeared after treatment. Patients are especially fond of calling this NED (No Evidence of Disease). Although this does not mean that the disease is cured, the symptoms have disappeared and the lymphoma cannot be detected using current tests. If this response is maintained for a long period, it is called a durable remission. The longer a patient is in remission the better the prognosis or outcome. However, as with other cancers, the disease could still possibly return and long-term follow-up is necessary.

 

Complete remission unconfirmed (CRu)

This term is used when all traditional methods of scanning show a complete remission, but there may still be something that is questionable. For example a lump that is still there, but shows negative by PET scan which means "most" likely scar tissue. Or ambiguous blood work. Or perhaps no follow up bone marrow biopsy to prove clear marrow. This is almost as good as complete remission but just leaves some room for doubt.


Molecular Remission

Sometimes (often in a clinical trial setting) advanced testing techniques are used to detect minute quantities of lymphoma. Usually it will be used on the bone marrow or blood. Some of these tests can detect just a single lymphoma cell in a sample of 10,000 cells or more. Some of the techniques used for such sensitive testing are Polymerace Chain Reaction, Flow Cytometry and DNA Microarray. When even these sensitive tests find no trace of lymphoma it is often called a molecular remission. This suggests a superior result to complete remission but nevertheless it is still possible to have a relapse after a molecular remission.

Partial remission

This term is used if the NHL is treated and the tumour shrinks to less than one-half of its original size

Improvement:

This term is used if the tumour shrinks following therapy but is still more than one-half of its original size. 

Stable disease:

The disease does not get better or worse following therapy.

Refractory

A cancer that is resistant to treatment. 

Prognosis

What is the likely outcome of the disease. Every patient wants to know their prognosis. It is just natural to want to know, even though doctors can only tell you statistically what is likely. They cannot tell you what will happen to you. Yet in the quest to better define the prognosis there exists the "IPI" below.  Use it with caution. It is designed to help define who is "at risk" of relapsing not who is going to die tomorrow morning.

The International Prognostic Index for aggressive lymphoma

An international index for aggressive NHL (diffuse large cell lymphoma) identifies 5 significant risk factors prognostic of overall survival. For each positive risk factor there is a greater risk of relapse. This index can also be applied to the indolent forms of Lymphoma but with a smaller degree of accuracy.

  • Age (<60 years of age versus >60 years of age)
  • Serum lactate dehydrogenase-LDH (normal versus elevated),
  • Performance status (0 or 1 versus 2-4), (see definition below)
  • Stage (I or II versus III or IV),
  • Extranodal site involvement (0 or 1 versus 2-4).

In the pre-Rituximab era patients with 2 or more risk factors have less than a 50% chance of relapse-free and overall survival at 5 years. However the proposed revised IPI indicates since the including of Rituximab with CHOP there are three distinct prognostic risk groups.

  • 0 risk factors, very good - 90% progression free survival @ 5 years
  • 1-2 risk factors, good - 80% progression free survival @ 5 years
  • 3-5 risk factors, poor - 50% progression free survival @ 5 years

The original IPI study from the New England Journal of Medicine

It has be suggested (2011) that instead of age 60 being the risk factor it should be raised to 70 due primarily to the benefit of adding Rituximab to therapy. This study was done using the R-CHOP-14 protocol in which R-CHOP is given every 14 days instead of 21.

Validation of the Elderly IPI (E-IPI) for Patients with Diffuse Large B Cell Lymphoma Using An Independent Data Set From the RICOVER-60 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)

There is a proposal for new new IPI by the National Comprehensive Cancer Network.  it uses the same 5 factors as above, but refines the definition paying more attention to the age and sites of involvement.  Since this new proposed NCCN-IPI uses the same factors it is easy to apply and discriminates the higher risk group more accurately. As of 2014 it is too soon yet to say if it will replace the IPI.

An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era

A Biologic Prognostic Model proposal

In the ever evolving world of advanced genetic testing, researchers are always trying to find more precise and more accurate ways to determine the prognosis for patients with DLBC, and hopefully to direct their therapy more accurately according to their prognosis.  To this end a new Biologic Prognostic Model (BPM) has also been proposed. Read the study below.

A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma

Read a peer review of the above study, "A promising new biologic prognostic model in diffuse large B-cell lymphoma "


 

The International Prognostic Index for Follicular NHL (FLIPI)

The FLIPI was proposed by an international cooperative group in 2004, and it pertains to follicular lymphoma, and perhaps to other low grade types as well. Each criteria scores one point. Less is better.

Click here to read the abstract from the Journal Blood.

  • Age (< 60 years of age versus >60 years of age)
  • Ann Arbor Stage III or IV
  • Haemoglobin level < 120 g/L
  • Elevated LDH
  • Greater than 4 nodal sites

* Note OS means Overall Survival


Risk group # of factors % 5 year OS % 10 year OS
Low 0-1 90.6 70.7
Intermediate 2 77.6 50.9
High 3 or higher 52.5 35.5

 

There is a proposal to update the FLIPI with a new index. It has not been adopted yet, but you can read the FLIPI2 proposal at the link below.

Follicular Lymphoma International Prognostic Index 2: A New Prognostic Index for Follicular Lymphoma Developed by the International Follicular Lymphoma Prognostic Factor Project


Mantle Cell Lymphoma International Prognostic Index

The MIPI identifies four risk factors for overall survival. For each factor your get points from zero up to 3. The maximum score is 11 points

Points Age ECOG PS LDH (ULN) WBC, 10^9/L
0 <50 0-1 <0.67 <6.700
1 50-59 - 0.67 - 0.99 6.700 - 9.999
2 60-69 2-4 1.0 - 1.49 10.000 - 14.999
3 ≥ 70 - ≥ 1.5 ≥ 15.000


ECOG PS = Eastern Cooperative Oncology Group performance status

LDHULN = lactic acid dehydrogenase institutional upper limit of normal

WBC = white blood cell count from the complete blood count

  • Low risk (0-3 points)
  • Intermediate risk (4-5 points)
  • High risk (6-11 points)

When the MIPI was applied to the 455 cases:

Risk group (points) % of patients Median survival 5 year overall
survival
   Low Risk (0-3) 44% Not reached 60%
   Intermediate (4-5) 35% 51 months 35%
   High (6-11) 21% 29 months 20%

 

Source: Bloodjournal article "Vol 111, No. 2, pp.558-565


Prognostic Index for peripheral T-cell lymphoma unspecified

This index identifies 4 significant risk factors for overall survival.

Read the published paper here

  • Age > 60, relative risk 1.732
  • Performance status >=2, relative risk 1.719
  • Elevated LDH, relative risk 1.905
  • Bone marrow involvement, relative risk 1.454

Add the risk factors above:

  • 0 adverse factors 5 year survival 62.3%, 10 year survival 54.9%
  • 1 adverse factor, 5 year survival 52.9%, 10 year survival 38.8%
  • 2 adverse risk factors, 5 year survival 32.9%, 10 year survival 18%
  • 3 or 4 adverse risk factors, 5 year survival 18.3%, 10 year survival 12.6%

Proposed International Prognostic Index for Waldenström Macroglobulinemia

  • Age > 65 years
  • Haemoglobin ≤ 100 x 10^9/L
  • ß2 Microglobulin > 3mg/L
  • Monoclonal IgM concentration > 7.0 g/dL
  1. Low risk: Age below 65 and 0 or 1 other risk factors
  2. Intermediate risk: Age over 65 OR 2 other risk factors with age under 65
  3. High risk: 3 or more risk factors of any kind
Risk category Median survival (months)
1 142.5
2 98.6
3 43.5

 

Read the full study proposal here


Proposed International Prognostic Index for Mycosis Fungoides and Sézary Syndrome

Four different risk factors are defined

  • Stage IV versus stage <IV
  • Age over 60
  • Large cell transformation
  • Elevated Lactate dehydrogenase (LDH)

Three different 5 year overall survival groups are defined according to the number of risk factors.

  1. Low risk: 0 or 1 risk factors 68%
  2. Intermediate risk: 2 or 3 risk factors 44%
  3. High risk: 4 risk factors 28%

Source: Journal of Clinical Oncology


Proposed International Prognostic Index for MALT lymphoma

There are 3 factors that are highly prognostic for outcome

  1. Age >70
  2. Ann Arbor stage III or IV
  3. Elevated LDH
Risk factors 5 year Event Free Survival
0 or 1 70%
2 56%
3 29%

 

Note: Event Free Survival (EFS) refers to any adverse event, not just relapse or death. For example a heart attack would count as an event.

Source Blood Journal


Performance status

Performance status in the aggressive IPI is defined as

Grade Description
0 Fully active, able to carry on all pre-disease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2 Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
3 Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4 Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5 Dead


So if you are 2-4 on this scale then you get one point on the IPI scale. If you are 0-1 on the Performance scale you get zero on the IPI. As you can see the goal is to have a low IPI score.
You may also hear of the Karnofsky score. It is a similar scoring system used to evaluate a patients overall performance. However it goes into more detail in an effort to more accurately evaluate a patient for general medical purposes. It is not used when calculating the IPI score above.
Click here to read the Karnofsky performace scale


Stem Cell Transplant Co-Morbidity Index

This index is used to identify co-morbid factors for Non Relapse Mortality (NRM) during a stem cell transplant.

Comorbidity Definition Score
Arrhythmia Atrial fibrillation or flutter, sick sinus syndrome, or ventricular arrhythmias   1
Cardiac Coronary artery disease, congestive heart failure, myocardial infarction, or EF 50%   1
Inflammatory bowel disease Crohn disease or ulcerative colitis   1
Diabetes Requiring treatment with insulin or oral hypoglycemics but not diet alone   1
Cerebrovascular disease Transient ischemic attack or cerebrovascular accident   1
Psychiatric disturbance Depression or anxiety requiring psychiatric consult or treatment   1
Hepatic mild Chronic hepatitis, bilirubin > ULN to 1.5 x ULN, or AST/ALT > ULN to 2.5 x ULN   1
Obesity Patients with a body mass index > 35 kg/m2   1
Infection Requiring continuation of antimicrobial treatment after day 0   1
Rheumatologic SLE, RA, polymyositis, mixed CTD, or polymyalgia rheumatica   2
Peptic ulcer Requiring treatment   2
Moderate/severe renal Serum creatinine > 2 mg/dL, on dialysis, or prior renal transplantation   2
Moderate pulmonary DLco and/or FEV1 66%-80% or dyspnea on slight activity   2
Prior solid tumour Treated at any time point in the patient's past history, excluding nonmelanoma skin cancer   3
Heart valve disease Except mitral valve prolapse   3
Severe pulmonary DLco and/or FEV1 65% or dyspnea at rest or requiring oxygen   3
Moderate/severe hepatic Liver cirrhosis, bilirubin > 1.5 x ULN, or AST/ALT > 2.5 x ULN   3

  1. Low risk - 0 points
  2. Intermediate risk - 1-2 points
  3. High risk - 3 or more points

Source information: Blood, 15 October 2005, Vol. 106, No. 8, pp. 2912-2919

 


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