Thought I would start a new thread instead of creating a long tangent on another.
My question was regarding the significance of the percentages in the FISH test next to the different abnormalities. My del(17p) had 5% abnormal next to it, while my t(11;14) had 9% abnormal next to it.
I just found this article about 17p research on this site. It mentions the prognostic power of the proportion of cells with the abnormality. This *might* pertain to my question.
U Painuly et al, "17p Deleted Multiple Myeloma: Clinical Outcomes and Predictive Factors For Acquisition Of 17p Deletion," ASH 2013 annual meeting, abstract 1846
From the abstract:
"Finally, we also examined the impact of the proportion of cells with del17p. The median proportion of PCs with 17p deletion was 86% (range 9-100%). Patients with >80% cells with del17p had an inferior survival compared to the rest (1.9 vs. 2.8 years, p=0.01).
Forums
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FingersCrossed - Name: FingersCrossed
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Oct 2014 (Smoldering)
- Age at diagnosis: 44
Re: Percentages in FISH test results - significance?
..If you look hard enough, you can find any number of articles that say:
t(11,14) confers a favorable outcome; a Neutral outcome; and a worse outcome (unfavorable); These range from 1990 to present. The Blood series ( Hematology) have a number of examinations / articles re: the question of favorable/ unfavorable and life expectancies.
I'm sure the same holds true for del 17 p (or q).
Indeed, UAMS / Barlogie, et al, published quite a number of articles re: del 17 p (or q) as part of their series on Total Therapy I-IV.
The percents will change--regardless. They are simply a "snap-shot" in time as to the levels involved. They are also subject to the effects of treatment(s).
If I understand your question(s) properly, I am unaware of articles/ studies that predictably posit that accurate predictions can be "baseballed" off of percentages, measured at any one time. I would think response to treatment would be more relevant to your inquiry ?
Good luck.
t(11,14) confers a favorable outcome; a Neutral outcome; and a worse outcome (unfavorable); These range from 1990 to present. The Blood series ( Hematology) have a number of examinations / articles re: the question of favorable/ unfavorable and life expectancies.
I'm sure the same holds true for del 17 p (or q).
Indeed, UAMS / Barlogie, et al, published quite a number of articles re: del 17 p (or q) as part of their series on Total Therapy I-IV.
The percents will change--regardless. They are simply a "snap-shot" in time as to the levels involved. They are also subject to the effects of treatment(s).
If I understand your question(s) properly, I am unaware of articles/ studies that predictably posit that accurate predictions can be "baseballed" off of percentages, measured at any one time. I would think response to treatment would be more relevant to your inquiry ?
Good luck.
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Rneb
Re: Percentages in FISH test results - significance?
Oh I hear you. I know that's just one article. The next article I find could say the complete opposite.
I'm just looking for any information I can about the FISH test. I'm just curious if there is any real significance to the percentages or if they are, as you say, just a snapshot of my condition. I saw them and just wondered what they meant. I can ask the specialist, I'm just impatient, waiting for my appointment.
I'm just looking for any information I can about the FISH test. I'm just curious if there is any real significance to the percentages or if they are, as you say, just a snapshot of my condition. I saw them and just wondered what they meant. I can ask the specialist, I'm just impatient, waiting for my appointment.
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FingersCrossed - Name: FingersCrossed
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Oct 2014 (Smoldering)
- Age at diagnosis: 44
Re: Percentages in FISH test results - significance?
Good question, FingersCrossed. You generally hear or read of patients being classified as having, or not having, a certain chromosomal mutation like del(17p), like it's some kind of yes or no thing.
So, for me, that raises the related question: What's the percentage cutoff that leads a physician to say that you have a certain mutation? If the mutation shows up in a really small percentage of the tested cells, like 0.1%, do you still "have it"? Or is there a threshold percentage of some sort?
In fact, I think that, in some senses, this is really the question you're asking. I don't think there is much research like the study you pointed out, which looks at whether the percentage of cells with a certain abnormality affects prognosis.
So, for me, that raises the related question: What's the percentage cutoff that leads a physician to say that you have a certain mutation? If the mutation shows up in a really small percentage of the tested cells, like 0.1%, do you still "have it"? Or is there a threshold percentage of some sort?
In fact, I think that, in some senses, this is really the question you're asking. I don't think there is much research like the study you pointed out, which looks at whether the percentage of cells with a certain abnormality affects prognosis.
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Jonah
Re: Percentages in FISH test results - significance?
Hi,
There are one or two articles I know about that might address your question:
#1: H Avet-Loiseau et al, "Long-Term Analysis of the IFM 99 Trials for Myeloma: Cytogenetic Abnormalities [t(4;14), del(17p), 1q gains] Play a Major Role in Defining Long-Term Survival," Journal of Clinical Oncology, June 1, 2012 (full text)
and
#2: H Avet-Loiseau et al, "Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome," Blood, April 15, 2007 (abstract) (full text pdf)
They state that more than 60% del(17p) cells gives lower overall survival, but not less than 60%.
Abstract (#1):
Purpose In multiple myeloma, many prognostic parameters have been proposed. However, all of these predict shorter survival. To identify patients with a longer life expectancy, we updated the data of patients treated in the IFM (Intergroupe Francophone du Myelome) 99-02 and 99-04 trials.
Patients and Methods A series of 520 patients was analyzed. Median follow-up was 90.5 months. To perform a comprehensive analysis of the major prognostic factors, we reanalyzed all patients for 1q gains [in addition to updating del(13), t(4;14), and del(17p) analyses].
Results It was possible to identify a subgroup of patients (representing 20% of total patients) with an 8-year survival of 75%. These patients were defined by the absence of t(4;14), del(17p), and 1q gain and β2-microglobulin less than 5.5 mg/L.
Conclusion We propose that all patients with newly diagnosed multiple myeloma be evaluated for these three chromosomal changes, not only to define high-risk patients but also to identify those with a longer life expectancy.
Abstract (#2):
Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p).
Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis.
Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.
There are one or two articles I know about that might address your question:
#1: H Avet-Loiseau et al, "Long-Term Analysis of the IFM 99 Trials for Myeloma: Cytogenetic Abnormalities [t(4;14), del(17p), 1q gains] Play a Major Role in Defining Long-Term Survival," Journal of Clinical Oncology, June 1, 2012 (full text)
and
#2: H Avet-Loiseau et al, "Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome," Blood, April 15, 2007 (abstract) (full text pdf)
They state that more than 60% del(17p) cells gives lower overall survival, but not less than 60%.
Abstract (#1):
Purpose In multiple myeloma, many prognostic parameters have been proposed. However, all of these predict shorter survival. To identify patients with a longer life expectancy, we updated the data of patients treated in the IFM (Intergroupe Francophone du Myelome) 99-02 and 99-04 trials.
Patients and Methods A series of 520 patients was analyzed. Median follow-up was 90.5 months. To perform a comprehensive analysis of the major prognostic factors, we reanalyzed all patients for 1q gains [in addition to updating del(13), t(4;14), and del(17p) analyses].
Results It was possible to identify a subgroup of patients (representing 20% of total patients) with an 8-year survival of 75%. These patients were defined by the absence of t(4;14), del(17p), and 1q gain and β2-microglobulin less than 5.5 mg/L.
Conclusion We propose that all patients with newly diagnosed multiple myeloma be evaluated for these three chromosomal changes, not only to define high-risk patients but also to identify those with a longer life expectancy.
Abstract (#2):
Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p).
Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis.
Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with β2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.
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asaryden - Name: asaryden
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: August 2010
- Age at diagnosis: 48
Re: Percentages in FISH test results - significance?
This especially helps me place those percentages into some context. In the second paper, the authors write:
To further complicate matters, I wonder how many of these prognostic tools are accurate for both younger patients (say, <60-65) and older patients (>60-65) at the same time.
For del(13) and del(17p), the prognostic impact was even greater if we split the patients presenting the deletions according to a cutoff of plasma cells presenting the abnormality. Serial analyses showed that the most powerful cutoffs were 74% for del(13) and 60% for del(17p). The median EFSs were 27 months (versus 39 months; P < .001) and 14.6 months (versus 34.7 months; P < .001), respectively, for patients with del(13) of 74% and greater and del(17p) of 60% and greater. Using these cutoffs, 59% of patients with del(13) of 74% and greater were alive at 41 months (versus 80%; P < .001), whereas the median OS was 22.4 months for patients with del(17p) of 60% and greater (versus 75% of patients alive if del(17p) was less than 60%; P < .001)."
To further complicate matters, I wonder how many of these prognostic tools are accurate for both younger patients (say, <60-65) and older patients (>60-65) at the same time.
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FingersCrossed - Name: FingersCrossed
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Oct 2014 (Smoldering)
- Age at diagnosis: 44
Re: Percentages in FISH test results - significance?
Dear Fingers crossed,
I think the important thing to determine is whether or not the plasma cells were isolated and purified prior to performing the FISH analysis. In other words, was the lab performing FISH on purified plasma cells or the entire white blood cell population in the bone marrow?
If the myeloma (plasma) cells were purified / enriched first and only 5% of the isolated plasma cells had the 17p deletion, this would be considered a better situation (although it would still mean that a small subpopulation of your disease harbors this abnormality). If the FISH was performed on the entire white blood cell fraction, it makes it difficult to know what percentage of plasma cells contain the 17p deletion. You can come up with an estimate based on the percentage of plasma cells in the bone marrow aspirate, but it is harder to use the data from the abstract you cited if the plasma cells were not purified.
I hope this helps.
Good luck!
Pete V.
I think the important thing to determine is whether or not the plasma cells were isolated and purified prior to performing the FISH analysis. In other words, was the lab performing FISH on purified plasma cells or the entire white blood cell population in the bone marrow?
If the myeloma (plasma) cells were purified / enriched first and only 5% of the isolated plasma cells had the 17p deletion, this would be considered a better situation (although it would still mean that a small subpopulation of your disease harbors this abnormality). If the FISH was performed on the entire white blood cell fraction, it makes it difficult to know what percentage of plasma cells contain the 17p deletion. You can come up with an estimate based on the percentage of plasma cells in the bone marrow aspirate, but it is harder to use the data from the abstract you cited if the plasma cells were not purified.
I hope this helps.
Good luck!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: Percentages in FISH test results - significance?
Thanks Dr. Voorhees,
Is there any way to tell that the plasma cells were isolated before doing the FISH test, other than calling the lab to ask?
On the FISH page, the report does mention that each probe analyzed 200 cells. Does anyone know if I can assume then that the plasma cells were isolated and purified, meaning the percentages are based solely off the plasma cells and not the entire population?
Is there any way to tell that the plasma cells were isolated before doing the FISH test, other than calling the lab to ask?
On the FISH page, the report does mention that each probe analyzed 200 cells. Does anyone know if I can assume then that the plasma cells were isolated and purified, meaning the percentages are based solely off the plasma cells and not the entire population?
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FingersCrossed - Name: FingersCrossed
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Oct 2014 (Smoldering)
- Age at diagnosis: 44
Re: Percentages in FISH test results - significance?
In the second article it says:
So it seems cells were isolated and purified.
Interphase cytogenetic analysis: After overnight shipment, mononuclear cells were separated by gradient density centrifugation (Ficoll-Hypaque; Eurobio, Les Ulis, France). Plasma cells were then purified using CD138-coated magnetic beads according to the manufacturer’s instructions (Miltenyi Biotec, Paris, France), enabling a plasma cell purity higher than 90% (controlled in each patient) as previously described.
So it seems cells were isolated and purified.
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asaryden - Name: asaryden
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: August 2010
- Age at diagnosis: 48
Re: Percentages in FISH test results - significance?
Thanks asaryden,
But I mean my lab. How do I know that the lab that did *my* biopsy analysis isolated and purified my myeloma cells? Otherwise, as Dr. Voorhees said, I can't compare my percentages to those in the research papers.
My biopsy report mentions that 200 cells were analyzed for my FISH report. I'm not sure if that is the isolation and purification procedure that would make my results comparable to the research papers.
But I mean my lab. How do I know that the lab that did *my* biopsy analysis isolated and purified my myeloma cells? Otherwise, as Dr. Voorhees said, I can't compare my percentages to those in the research papers.
My biopsy report mentions that 200 cells were analyzed for my FISH report. I'm not sure if that is the isolation and purification procedure that would make my results comparable to the research papers.
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FingersCrossed - Name: FingersCrossed
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Oct 2014 (Smoldering)
- Age at diagnosis: 44
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