Serum Ferritin - A Tumor Marker for Malignant Lymphoma? (Part 2 of 2)

[Guest guest]

LONG article regarding iron and Lymphoma

--- Sue92195@... wrote:

)

> From: Sue92195@...

> Date: Wed, 11 Jul 2001 02:29:25 EDT

> Reply-to: Copper-Depletion

> Subject: [Copper-Depletion] Serum Ferritin - A

> " Tumor Marker " for Malignant Lymphoma?

>

> I have finished my translation of a medical article

> written in German about

> lymphoma (cancer of the immune system) and

> elevations of ferritin blood

> levels. Please keep in mind, this is an amateur

> translation which is surely

> not perfect. We have tried hard to retain the exact

> meanings of the original

> investigators, but there are no guarantees of the

> translation accuracy. I

> used a scanner, lots of special character needed

> manual corrections, and an

> on-line German translator for a start. Then I had a

> lot of help from two of

> my German lymphoma friends at nhl-info to whom I

> give my hearty thanks.

>

> The two-column Word for Window version with German

> on left and the English

> translation on the right is in the group files

> section or attached to this

> e-mail.

>

>

=========================================================

>

>

> Original Papers

> Onkologie 1990;13:102-108

>

> Serum Ferritin - A " Tumor Marker " for Malignant

> Lymphoma?

>

> Aulbert(a), O. Steffens(

>

> (a) Ev. Waldkrankenhaus Spandau, Akademisches

> Lehrkrankenhaus d. Freien

> Universität Berlin

> ( Innere Klinik und Poliklinik (Tumorforschung),

> Westdeutsches

> Tumorzentru, Universitätsklinikum Essen

>

> Summary and Key Words

>

> Serum ferritin concentration as a tumor marker

> was investigated in 535

> patients with malignant lymphomas. The study

> included 207 patients with

> Hodgkin disease, 196 patients with low grade

> non-Hodgkin lymphoma and 132

> patients with high grade non-Hodgkin lymphoma of

> different tumor stages.

>

> Increased serum ferritin concentrations were

> found in 54% of the

> patients. When we divided the group according to

> disease stage, we then

> found serum ferritin concentration was elevated in

> 12.3% of patients with

> stage I, in 33.8% of patients with stage II, in

> 72.2% of patients with stage

> III and in 94% of patients with stage IV. The serum

> ferritin levels

> correlated with the tumor mass. There was no

> significant difference between

> Hodgkin lymphoma and non-Hodgkin lymphoma.

>

> Patients with concomitant hepatocellular

> disease and also patients in

> chemotherapy had high levels of serum ferritin. In

> patients with low grade

> malignant non-Hodgkin lymphoma which included bone

> marrow infiltration, serum

> ferritin levels correlated better with the tumor

> stages according to Rai

> (Endnote A) than with the Ann Arbor classification.

>

> The serum ferritin concentration closely

> followed the activity of the

> disease. Ferritin levels dropped with cancer

> treatment, and patients

> achieving complete remissions normalized their serum

> ferritin levels. With

> tumor relapse or tumor progression, serum ferritin

> levels increased again.

>

> The data suggest that the serum ferritin

> concentration can be used for

> monitoring cancer condition of patients with

> malignant lymphoma. Because of

> its limited specificity and low sensitivity, it

> cannot be used as a screening

> test. Nevertheless, it is a helpful additional

> parameter for the control of

> the activity of the disease.

>

> Ferritin - Malignant Lymphoma - Tumor Marker - Tumor

> Stage

>

> Introduction

>

> Along with hemosiderin (insoluble iron

> storage), ferritin represents the

> substantial intracellular iron-binding protein [1].

> It can be found in almost

> every part of the human body, above all however in

> the liver, spleen, and

> bone marrow. In small quantities, it is also in the

> circulating blood. Its

> concentration amount is normally 20-150 ng/ml [2].

> Serum ferritin

> concentration represents a very reliable measure for

> the storage iron. The

> correlation between serum ferritin concentration and

> iron storage is so

> accurate that 1 ng/ml ferritin blood serum is

> equivalent to F-10 mg storage

> iron [2-9]. Accordingly primary or secondary iron

> overload statuses are

> partially characterized by substantial increases in

> the serum ferritin

> concentration by [10-14].

>

> Increased serum ferritin concentration is also

> found during inflammatory

> illnesses and infections [15-17]. Here the ferritin

> has obviously the meaning

> acute phase protein, just like other tests

> representing systemic response to

> inflammation -- Lactic Dehydrogenase (LDH),

> C-Reactive Protein (CRP),

> Fibrinogen (a soluble plasma protein), Haptoglobin

> (a plasma protein

> increased in certain inflammatory disorders) or the

> BSG [blut Senkungs

> Geschwinidigkeit, blood / separating or going down /

> speed OR speed of

> separation of the blood].

>

> Recently, elevated serum ferritin

> concentrations were also found in

> various tumor illnesses. With certain forms of

> leukemia, increased serum

> ferritin is a genuine tumor marker [18, 19].

> However, since elevated serum

> ferritin can also indicate increased iron storage,

> the acceptance of serum

> ferritin as either a " tumor-associated marker " or as

> an " acute phase protein "

> with solid tumor cancers is still being

> controversially discussed [20-27, 32].

>

> Lymphatic system illnesses seem to be a special

> case [10, 22, 26-33].

> Thus, with Hodgkin’s disease, the lymphocytes in

> the stricken spleen and also

> the peripheral blood show an increased ferritin

> synthesis and secretion

> [28-31], however, this data did not remain without

> contradiction [27, 33].

> Accordingly the cause of increased concentrations of

> serum ferritin with

> malignant lymphoma is not settled. The present study

> examines the serum

> ferritin concentrations of 535 patients with

> non-Hodgkin lymphoma and with

> Hodgkin’s lymphoma as well as their dependency of

> the degree of tumor

> propagation and of progression of disease.

>

> Methods

>

> Criteria of patients selected in the study

>

> Patients with malignant lymphomas of various

> histological types and

> various degrees of tumor propagation were examined.

> Patients were excluded

> from the investigation if their disease was

> accompanied by blood loss in the

> intestine, the urinary passage or the genitals;

> patients with liver

> illnesses, which accompanied with

> laboratory-chemically understandable liver

> cell decay or with protein synthesis disturbances,

> with renal protein losses,

> characters of a infection or a inflammation

> reaction, with several preceded

> blood transfusions with higher grade transformations

> or parenteral

> (intravenous) nutrition.

>

> Laboratory tests

>

> All hematological and chemical measurements

> were performed in the

> laboratories of the internal hospital and health

> center (tumor research) of

> the university clinic in Essen, the West German

> tumor center, as well as in

> the central laboratory of the St. Barbara Hospital

> in Gladbeck. Ferritin,

> transferrin, iron, GOT, GPT, gamma GT, LDH, total

> protein, creatinine and

> urea were all measured by peripheral blood testing.

>

> Measurement of Ferritin

>

> The serum ferritin concentrations were measured

> by an enzyme immunoassay

> (12). A commercially available enzyme immnoassay was

> used (Ferrizyme of

> Abbott Labs). The ferritin serum levels were charted

> and shown as standard

> curves of ferritin concentration. The average,

> which was determined at 60

> healthy persons was 45 ng/ml (18-114 ng/ml) in

> females and 83 ng/ml (28-186

> ng/ml) in males.

>

> Histological Investigation

>

> The histological and cytotoxic analysis of the

> tumor sample was performed in

> pathological Institute of the University Clinic as

> well as parallel to it in

> pathological Institute of the University of Kiel

> (lymphoma register). The

> non-Hodgkin lymphoma was classified according to the

> Kieler Classification

> System (Endnote C) [3-4].

>

> Determination of the Tumor Mass

>

> The classification of the tumor mass was

> differentiated from + to +++++.

> The tumor propagation of the lymphomas were

> subdivided into the tumor stages

> I-IV after either the Ann Arbor (Endnote [35] or

> the Rai (Endnote A)

> classification [36].

>

> Results

>

> Clinical levels of the serum ferritin

> concentration in relationship to

> tumor propagation were evaluated to determine if

> ferritin level could be a

> tumor associated marker with lymphatic system

> illnesses. We analyzed the

> serum ferritin level in 535 patients with malignant

> lymphoma who were

> monitored or treated in the years 1983-1988 and

> related the results to the

> disease tumor progression. In a second step we

> examined different

> interference factors which limit the value of serum

> ferritin concentration as

> indicator for the tumor propagation. Beyond that we

> continually monitored

> serum ferritin concentration over the entire disease

> process and related it

> with the proliferation activity the lymphatic tumor

> illness.

>

> The Dependency of the Serum Ferritin Concentration

> on the Tumor Propagation

>

> From the patients examined by us, there were

> 207 with Hodgkin’s

> lymphoma, 196 with low-grade non-Hodgkin’s

> lymphoma, and 132 with high-grade

> non-Hodgkin lymphoma. Pathologically increased

> serum ferritin concentrations

> were found in the stage I by 12.3%, in the stage II

> by 33.8%, in the stage

> III by 72.7% and in the stage IV by 94% of the

> patients. There was not a

> significant difference between the patients with

> Hodgkin disease and those

> with non-Hodgkin lymphoma. The serum ferritin

> concentration rose with

> increasing tumor propagation on (table 1, picture 1)

> While there was only a

> very slight tendency toward hyperferritinemia (high

> ferritin) in the stages

> I and II, the serum ferritin concentration in the

> tumor stage III was

> significantly for over the standard value. Even

> higher serum ferritin

> concentration showed up in the stage IV. On the

> other hand, patients who

> achieved a full remission again displayed normal

> serum ferritin concentration.

>

> Table 1 Serum Ferritin Concentration in patients

> with untreated malignant

> lymphomas (n=535).

>

> Hodgkin n

>

> Stage I 90 ± 4T ng/ml 28

> Stage II 138 ± 65 ng/ml 44

> Stage III 256 ± 108 ng/ml 28

> Stage IV 490 ± 144 ng/ml 24

> Full Remission 72 ± 45 ng/ml 83

>

> Non-Hodgkin-L. n

>

> Stage I 68 ± 43 ng/ml 56

> Stage II 124 ± 51 ng/ml 43

> Stage III 214 ± 117 ng/ml 48

> Stage IV 719 ± 360 ng/ml 69

> Full Remission 61 ± 43 ng/ml 112

>

> * Standard deviations

>

>

> Disrupted correlation between serum ferritin

> concentration and tumor

> propagation

>

> The observations of increased serum ferritin

> concentrations with

> different malignant tumors and inflammatory

> illnesses suggests that it is not

> a specific tumor-associated marker for lymphatic

> system illnesses. During our

> investigations different interference factors

> presented themselves, which

> limited the clinical value of the serum ferritin

> concentration as a

> tumor-associating marker

>

> Elevated serum ferritin concentration under a

> chemotherapy:

>

> Ferritin is present in the blood serum in very

> low concentration

> compared with total body’s stores of ferritin. So,

> serum ferritin

> concentration can quickly rise by release of

> ferritin from damaged cells.

> Such a situation is conceivable in the context of

> chemotherapy. Therefore, we

> have measured the serum ferritin concentration in

> patients with malignant

> lymphoma directly before and during any tumor

> fighting therapy (chemotherapy,

> radiation, etc.)

>

> A clear elevation of the serum ferritin

> concentration was observed under

> chemotherapy (fig. 2). It is remarkable that the

> increase of ferritin during

> chemotherapy was more pronounced in those patients

> whose initial

> concentration serum ferritin was the highest before

> being treated. These

> findings show that the extent of the serum ferritin

> increases under a

> chemotherapy depends upon the serum ferritin

> concentration before the patient

> has been treated - and thus correlates with the

> tumor stage or the tumor

> mass.

>

> Elevated, high serum ferritin concentrations

> are found in the present a

> hepatocellular damage: As the most substantial iron

> storage organ, the liver

> indicates a particularly high content of

> intracellular ferritin. The question

> therefore arises to what extent liver cell damage

> also accompanying limits

> the usability of the serum ferritin in concentration

> with malignant

> lymphomas. In order to check this, we examined our

> patients with both

> conditions of malignant lymphoma and simultaneous

> liver cell damage. In

> figure 3 the patients, whose pathologically

> increased laboratory-chemical

> parameters (GOT. GPT, Gamma GT) of liver damage,

> individually according to

> their tumor stage. It is remarkable that the serum

> ferritin concentration of

> these patients was elevated over the tumor-dependent

> serum ferritin

> concentration of the other lymphoma patients.

>

> These findings show that when there is more

> hepatocellular damage the

> correlation between serum ferritin concentration and

> tumor propagation degree

> is faulty.

>

> Deviations of serum ferritin level in relationship

> to lymphoma stage depended

> upon the classification system used:

>

> Remarkably low serum ferritin concentrations

> became apparent in a number

> of early low grade non-Hodgkin’s lymphoma patients

> categorized as Stage IV by

> the Ann Arbor criteria [47] only because of bone

> marrow involvement or

> categorized as Stage III only because of the spread

> of cancer which is still

> at a minimal disease level. As can be seen in

> figure 4, these values were

> clearly under the appropriate ferritin

> concentrations of other lymphomas in

> Stage III or IV.

>

> This apparent lack of correlation between serum

> ferritin concentration

> and tumor propagation could be avoided when these

> patients were staged

> according to the Rai Classification System (Endnote

> A) [36]. This

> classification is preferable for lymphomas

> infiltrating the bone marrow as

> it uses the lymphatic marrow infiltration on the

> blood formation and

> therefore takes into consideration the tumor mass.

>

> The correlation of the serum ferritin concentration

> with the disease process

>

> As a further step, we examined, to what extent

> the serum ferritin

> concentration can be a measurement of disease

> progression with patients with

> malignant lymphoma. We measured the serum ferritin

> concentrations during the

> entire duration of the disease and compared these

> with the disease progress

> Figure 5 shows serum ferritin movements of patients

> during primary induction

> therapy. It can be observed that a decline of

> elevated serum ferritin levels

> parallel the therapy-induced remission. The amount

> of decrease in serum

> ferritin is not dependent upon of the prior

> elevation level of the untreated

> lymphoma patient’s serum ferritin nor is it

> dependent on initial tumor stage.

> With achieving a full remission, serum ferritin

> concentration completely

> normalized.

>

> During further disease progression, serum

> ferritin concentrations were

> monitored and showed that a lymphoma relapse was

> accompanied by increasing

> serum ferritin concentration (fig. 6). If

> additional chemotherapy induced

> another remission, the serum ferritin levels were

> again decreased. If the

> tumor progression was therapeutically not

> controllable, the serum ferritin

> concentration continued to rise uninfluenced by

> therapy. These results show

> that the serum ferritin concentration is a useful

> parameter for process

> evaluation of our patients.

>

> Discussion

>

> So far, no specific tumor associated marker is

> well-known for malignant

> Hodgkin’s disease or non-Hodgkin lymphoma. For

> diagnostic assistance with

> the care of patients with malignant lymphomas, one

> fell back on the

> relatively nonspecific markers or acute phase

> proteins, for example the blood

> corpuscle lowering rate, the lactic dehydrogenase

> (LDH), the Haptoglobin (a

> protein binding to hemoglobin which is decreased in

> certain inflammatory

> disorders), ferritin, and beta-2 microgloblin.

>

> The problem with these markers, however, is

> their small sensitivity

> which does not support early diagnosis of disease. A

> measurable elevation of

> these markers usually takes place only during a

> large tumor propagation, and

> even then the elevations largely overlaps normal

> levels. Besides this,

> specificity is also limited since we know situations

> other than lymphoma can

> cause modification of these parameters.

>

> Observations from this study point toward the

> fact that the serum

> ferritin concentration represents a clinically

> useful diagnostic parameter

> with malignant lymphomas [10, 15, 26-33], and

> additionally, with other

> different malignant tumors [20-25]. In the majority

> of the investigations,

> the serum ferritin concentration correlates with the

> tumor mass and with the

> process of the illness. On the other hand , other

> diseases have been shown to

> be accompanied by increased ferritin levels [2-9]

> Also, liver cell damage or

> inflammation could cause increase in [15-17] serum

> ferritin concentration.

>

> The first step in our investigation was to

> measure untreated lymphoma

> patients for their serum ferritin concentration in

> relationship to tumor

> stage. The serum ferritin concentrations of

> untreated lymphoma patients were

> increased in 54% of the cases. The serum ferritin

> concentration increased in

> relationship with increasing tumor propagation

> (table 1, fig. 1).

>

> Our data is confirmed by the reports of other

> groups which found

> increased serum ferritin concentrations with

> malignant lymphomas [26, 27, 33,

> 38-40]. These studies also showed that in both

> Hodgkin’s and non-Hodgkin’s

> lymphoma, increasing tumor propagation was

> accompanied by rising serum

> ferritin concentration, elevations significantly

> above the normal range

> especially in the tumor stages III and IV. The

> cause for this

> hyperferritinemia was thereby attributed to a

> disturbance of the iron

> metabolism with an increase of the RES ferritin

> store [26]. (See Endnote E)

>

> In order to be able to measure the specificity

> of the hyperferritinemia

> with malignant lymphomas, different factors were

> examined, which disturb the

> relationship between the serum ferritin

> concentration and the tumor status.

> These factors have to be known to assess and

> evaluate this tumor marker.

>

> There are indications that malignant tumor cells can

> both elevate and

> decrease levels of serum ferritin. Thus, it has

> been shown that tumor cells

> in vitro synthesize ferritin [41].Also in breast

> cancer tissue, ferritin

> could be proven by Immune fluorescence [42]. The

> direct proof of a increased

> ferritin synthesis held true for leukemia cells [18,

> 19, 43]. Likewise it

> could be shown that normal lymphocytes as well as

> malignant lymphatic cells

> synthesize and contain ferritin at higher

> concentrations [28, 30].

>

> The question therefore arises, could some of the

> disintegrating lymphatic

> cells release measurable quantities of intercellular

> ferritin which causes an

> increase of the serum ferritin concentration. This

> question is of importance,

> since patients mostly undergo chemotherapy during

> the active phase of the

> disease, and, in such cases, increased serum

> ferritin concentration cannot

> always be associated with tumor activity.

>

> Therefore, we compared the serum ferritin

> concentration of our untreated

> lymphoma patients with that of the lymphoma patients

> currently under

> chemotherapy. In all cases, there was a clear

> elevation of serum ferritin

> with patients in chemotherapy. This increased

> elevation was more pronounced

> in cases with larger tumor mass. (fig. 2).

>

> These findings agree with other reports that

> high intracellular ferritin

> concentration exist in tumor cells and in lymphoma

> cells [22, 31, 39, 43-45].

> They indicate that the rise of the serum ferritin

> concentration actually

> originates by the release of ferritin from

> intracellular lymphatic cells.

> This would explain why larger tumor masses release

> more ferritin during

> successful chemotherapy treatments. On the other

> hand, these findings lead to

> the conclusion that while currently under

> chemotherapy, level of serum

> ferritin does not relate to tumor propagation or the

> activity of the disease.

>

> Increased serum ferritin concentration with

> chronic and acute liver

> illnesses has been observed [9, 17, 37, 38]. This is

> based on the fact that

> this hyperferritinemia is to be explained by an

> increased release of ferritin

> from damaged liver cells. Considering the

> extraordinarily low physiological

> serum ferritin concentration in the blood, it is to

> be expected that a such a

> ferritin release from the damaged liver tissue leads

> to measurable increase

> in serum ferritin concentration [1, 37]. On the

> other hand the liver

> represents also the reduction organ for the

> ferritin, so that a liver cell

> damage can also be accompanied with a decreased

> reduction rate and so cause

> an increase of the serum ferritin concentration

> [46].

>

> In malignant lymphatic system illnesses, we

> observe liver cell damage

> due to direct infiltration of lymphoma in the liver

> or due to hepatoxic

> therapy. With the examination of this connection

> (fig. 3) high serum ferritin

> concentration were found elevated in all cases even

> comparing the ferritin

> values to comparable patients with the same degree

> of tumor propagation

> without simultaneous liver damage. This data agreed

> with identical findings

> of other authors [38] and to demonstrated that in

> such situations of liver

> damage, the serum ferritin concentration could not

> be used as a

> tumor-associated marker.

>

> A dependency of the serum ferritin in

> concentration of the histological

> type of the non-Hodgkin lymphoma has already been

> described by some other

> authors [47]. Other authors could find no

> relationship between the

> histological type and the elevation of the serum

> ferritin concentration [27,

> 48]. Also, we found with a part of the patients with

> low grade lymphomas of

> the tumor stages III and IV after the Ann Arbor

> classification [35],

> inadequate low serum ferritin concentration clearly

> under the values of other

> histological lymphoma types of same tumor stages

> (fig. 4). These were mainly

> cases of low grade non-Hodgkin’s lymphoma (NHL),

> partially with a very

> early generalized propagation of lymph nodes, and

> which had to be attributed

> to the Ann Arbor classification Stage III, even if

> these lymph nodes were

> still small. The same applied also to patients, with

> whom according to the

> biological characteristics of low grade lymphoma had

> a bone marrow

> involvement who were classified Stage IV from the

> beginning by the Ann Arbor

> system, even if the degree of the marrow

> infiltration, i.e. the tumor mass,

> was not yet particularly pronounced. In these

> cases, a discrepancy between

> the tumor stage is present by the Ann Arbor

> classification and of the actual

> tumor mass.

>

> Unlike to the Ann Arbor classification system,

> [35] the Rai

> classification (Endnote A) [36] corresponds more to

> certain blood parameters

> and the actual size of tumor mass. Thus, if one

> applies the Rai

> classification (Endnote A) to this kind of

> non-Hodgkin lymphoma with bone

> marrow involvement, then better correlations show up

> between the serum

> ferritin concentration and the tumor propagation.

>

> During the evaluation of ferritin as a tumor

> marker, the question arises

> whether changes of tumor growth show up clearly and

> fast enough and in

> measurable modifications of the serum ferritin

> concentration and whether

> these modifications of the serum ferritin

> concentration occur early enough to

> be clinically usable.

>

> In this connection it could be shown that the

> early achieved tumor

> regression was accompanied by a decrease in serum

> ferritin concentration.

> When a full remission was achieved, a complete

> normalization of the serum

> ferritin concentration occurred (fig. 5). A relapse

> or a renewed tumor

> progression was accompanied by a renewed

> elevation of the serum

> ferritin concentration. The change of the serum

> ferritin concentration

> occurred not substantially before other proven tumor

> markers and therefore

> cannot be used as a reliable early symptom, but only

> as one among several

> parameters. Our investigations are acknowledged by

> other working groups. As a

> cause an increased synthesis and secretion of

> ferritin from the lymphatic

> cells was assumed here. Also with patients with

> acute lymphoblastic leukemia

> (ALL) a rise of the serum ferritin concentration

> showed up with progressive

> tumor growth and a normalization of serum ferritin

> concentration when

> achieving a full remission. The explanation for this

> is likewise an increased

> synthesis and release of intracellular ferritin from

> the leukemic lymphatic

> cells [22, 28, 31, 49-51].

>

> Our findings of a close relationship between

> serum ferritin

> concentration and tumor mass or the proliferation of

> the illness and also in

> a particular rise of the serum ferritin

> concentration for the patient under a

> cytotoxic chemotherapy allows the conclusion that

> hyperferritinemia is caused

> by increased synthesis and release of ferritin from

> the malignant cells. This

> does not exclude the possibility that the release of

> ferritin as a

> nonspecific response of the RES (See endnote E) in

> the sense of one " acute

> phase proteins " plays a certain role. Apparently

> monocytes are responsible

> for the secretion of ferritin in this case [27, 52].

> Similar processes seem

> also to be the cause of hyperferritinemia with

> chronic infections [15-17]. On

> the other hand observations exist according to which

> the hyperferritinemia is

> interpreted with malignant tumors as indicator for

> an increased RES (see

> endnote E) ferritin storage. As a cause for this a

> perturbated iron release

> from the RES [26, 40] or a rearrangement of the iron

> of the perturbated

> Erythropoiesis (Endnote D) into the RES ferritin

> storage is being considered

> as a possibility [32]. This tumor-conditioned

> disturbance of transferrin and

> iron metabolism leads to an iron-overload of storage

> iron and thereby to a

> hyperferritinemia, which correlates with the extent

> of the tumor illness

> [32]. Possibly are situated also several of these

> causes the rise of the

> serum ferritin concentration with patients with

> malignant lymphomas as the

> base [33, 39].

>

> Our data show that serum ferritin concentration

> is a useful additional

> parameter with the care of patients with malignant

> lymphomas. Due to the

> smaller specificity and low sensitivity of serum

> ferritin levels, it should

> remain as a monitoring devise after diagnosis of

> lymphoma has been confirmed.

> It must be realized that hyperferritinemia has

> other cause (blood

> transfusions, liver cell damage, chronic

> Inflammations or infections) which

> must always be excluded [1]. Unfortunately,

> elevation of the serum ferritin

> concentration does not show early in the disease

> process. Rather the changes

> in serum ferritin levels follow parallel to the

> tumor progression or to tumor

> recovery and serve as an additional accompanying

> parameter for the process of

> evaluating malignant lymphoma.

>

>

>

>

>

>

>

>

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