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Rituximab associated neutropenia: description of three cases and an insight into the underlying pathogenesis.

Weissmann-Brenner A, Brenner B, Belyaeva I, Lahav M, Rabizadeh E - Med. Sci. Monit. (2011)

Bottom Line: Control plasma did not have such an effect.After recovery the patient's plasma did not inhibit colony formation, similar to control.RAN is a clinically significant side effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Israel. alinabrenner@yahoo.com

ABSTRACT

Background: To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism.

Case report: We describe three patients with RAN. The effect of patient's plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient's plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient's cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient's plasma did not inhibit colony formation, similar to control.

Conclusions: RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity.

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Related in: MedlinePlus

The effect of patient’s cell supernatant (s) on colony formation. The effects of patient’s mononuclear cells supernatant, induced by PHA at neutropenia and after recovery, were tested on a healthy BM for (GM) colony formation. The cell supernatant of a healthy donor was used as control. The results are expressed as percent of control and mean ±SD of three independent experiments, each of them performed in triplicate. Ps: Patients’s cells supernatant, Ds: Donor’s cells supernatant, s: PHA supernatant (without cells).
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f3-medscimonit-17-11-cs133: The effect of patient’s cell supernatant (s) on colony formation. The effects of patient’s mononuclear cells supernatant, induced by PHA at neutropenia and after recovery, were tested on a healthy BM for (GM) colony formation. The cell supernatant of a healthy donor was used as control. The results are expressed as percent of control and mean ±SD of three independent experiments, each of them performed in triplicate. Ps: Patients’s cells supernatant, Ds: Donor’s cells supernatant, s: PHA supernatant (without cells).

Mentions: The effect of the patient’s plasma on CFU growth was measured by the addition of 50 μl plasma to the culture of a healthy BM immersed in methylcellulose. In the leukopenic period (WBC 790/mm3), the patient’s plasma inhibited CFU growth completely (0 colonies), whereas the addition of healthy plasma did not change the number of colonies grown spontaneously from a healthy BM (125±4.3) (Figure 2). In order to investigate the role of cell secretion in CFU inhibition, the patient’s cells and donor’s cells were incubated for 72 hours in the presence of 2.5% PHA. As a baseline (control), PHA supplemented medium was also incubated with the cells. The addition of 10 μl/well of the supernatants to the methylcellulose culture of 105 per well BM cells, did not change the number of CFU, which resembled their quantity in all cases: patient’s plasma, donor’s plasma and PHA (116±17, 114±12 and 115±5.2 CFU, respectively). This observation suggests that the secretion of cells do not have any function in the inhibition of colony formation (Figure 3).


Rituximab associated neutropenia: description of three cases and an insight into the underlying pathogenesis.

Weissmann-Brenner A, Brenner B, Belyaeva I, Lahav M, Rabizadeh E - Med. Sci. Monit. (2011)

The effect of patient’s cell supernatant (s) on colony formation. The effects of patient’s mononuclear cells supernatant, induced by PHA at neutropenia and after recovery, were tested on a healthy BM for (GM) colony formation. The cell supernatant of a healthy donor was used as control. The results are expressed as percent of control and mean ±SD of three independent experiments, each of them performed in triplicate. Ps: Patients’s cells supernatant, Ds: Donor’s cells supernatant, s: PHA supernatant (without cells).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539507&req=5

f3-medscimonit-17-11-cs133: The effect of patient’s cell supernatant (s) on colony formation. The effects of patient’s mononuclear cells supernatant, induced by PHA at neutropenia and after recovery, were tested on a healthy BM for (GM) colony formation. The cell supernatant of a healthy donor was used as control. The results are expressed as percent of control and mean ±SD of three independent experiments, each of them performed in triplicate. Ps: Patients’s cells supernatant, Ds: Donor’s cells supernatant, s: PHA supernatant (without cells).
Mentions: The effect of the patient’s plasma on CFU growth was measured by the addition of 50 μl plasma to the culture of a healthy BM immersed in methylcellulose. In the leukopenic period (WBC 790/mm3), the patient’s plasma inhibited CFU growth completely (0 colonies), whereas the addition of healthy plasma did not change the number of colonies grown spontaneously from a healthy BM (125±4.3) (Figure 2). In order to investigate the role of cell secretion in CFU inhibition, the patient’s cells and donor’s cells were incubated for 72 hours in the presence of 2.5% PHA. As a baseline (control), PHA supplemented medium was also incubated with the cells. The addition of 10 μl/well of the supernatants to the methylcellulose culture of 105 per well BM cells, did not change the number of CFU, which resembled their quantity in all cases: patient’s plasma, donor’s plasma and PHA (116±17, 114±12 and 115±5.2 CFU, respectively). This observation suggests that the secretion of cells do not have any function in the inhibition of colony formation (Figure 3).

Bottom Line: Control plasma did not have such an effect.After recovery the patient's plasma did not inhibit colony formation, similar to control.RAN is a clinically significant side effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Israel. alinabrenner@yahoo.com

ABSTRACT

Background: To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism.

Case report: We describe three patients with RAN. The effect of patient's plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient's plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient's cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient's plasma did not inhibit colony formation, similar to control.

Conclusions: RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity.

Show MeSH
Related in: MedlinePlus