Immature reticulocytes as an early predictor of engraftment in autologous and allogeneic bone marrow transplantation

Noronha, José F. A.; Souza, Cármino Antônio de; Vigorito, Afonso Celso; Aranha, Francisco; Zulli, Roberto; Miranda, Eliana Cristina Martins; Grotto, Helena Zerlotti Wolf

doi:10.1046/j.1365-2257.2003.00486.x

Cited by 38 publications

(29 citation statements)

References 20 publications

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“…These studies however, utilized different methods for measuring immature reticulocytes and/or compared the IRF to ANCX500/ml and not to the more clinically relevant ANCX100/ml (Table 4). 10,[15][16][17][18][19][20][21][22] Since there are different types and manufacturers of blood count analyzers with different reference values and calibration parameters, 9,23 end points such as doubling (IRF-D) or normalization (IRF-N) of the IRF can be used regardless of equipment and would simplify and standardize result interpretation among investigators.…”

Section: Discussionmentioning

confidence: 99%

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

Grazziutti

Lei

Miceli

et al. 2006

Bone Marrow Transplant

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The duration of neutropenia (absolute neutrophil count (ANC) p100/ll) identifies cancer patients at risk for infection. A test that precedes ANCX100/ll would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANCX100/ll in 99% of patients after the first Mel-ASCT by (mean7s.d.) 4.2371.96 days and in 97% of the patients after the second Mel-ASCT by 4.1171.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte countX100/ll to the time to ANCX100/ll. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANCX100/ll.

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Section: Discussionmentioning

confidence: 99%

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

Grazziutti

Lei

Miceli

et al. 2006

Bone Marrow Transplant

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“…(10) and Eq. (11) results in: (12) with: (13) Extension to time variant cellular disposition parameters-Next consider the case where the cellular disposition parameters are time variant. That is, the residence time in the systemic circulation, 'b − a', is a function of time.…”

Section: Theoretical Considerationsmentioning

confidence: 99%

“…Measurement of the reticulocyte count is valuable for determining if a patient has a functionally normal response to either endogenously produced or exogenously administered erythropoietin (Epo) [5,8]. Reticulocyte counts are also used to monitor bone marrow suppression by chemotherapy [9] and bone marrow engraftment following bone marrow transplantation [10][11][12][13]. The maturation of erythroid progenitor cells into reticulocytes and ultimately RBCs is primarily controlled by Epo, a-35kD glycoprotein hormone produced by the pertibular cells of the kidney in response to oxygen need [1].…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic analysis of time-variant cellular disposition: reticulocyte disposition changes in phlebotomized sheep

Freise

Widness

Schmidt

et al. 2007

J Pharmacokinet Pharmacodyn

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Most pharmacodynamic (PD) models of cellular response assume a time-invariant (i.e., constant) cellular disposition despite known changes in the disposition with time, such as the reticulocyte residence time in the systemic circulation during stress erythropoiesis. To account for changes in cellular disposition, a comprehensive PD model that involves endogenous erythropoietin (Epo), reticulocytes, and hemoglobin responses was developed in phlebotomized sheep that considers a time-variant reticulocyte residence time and allows for the simultaneous determination of changes in the cellular disposition and cellular production. Five sheep were phlebotomized to hemoglobin concentrations of approximately 4 g/dl. Epo concentrations, reticulocytes, and hemoglobin concentrations were frequently sampled for 5-7 days prior to and 25-30 days following the phlebotomy. Initial steady-state conditions were assumed and the time-variant reticulocyte residence time in the systemic circulation was semiparametrically represented using a constrained spline function. Hemoglobin production was modeled using a Hill function via an effect site compartment. The initial steady state reticulocyte residence time in the systemic circulation was estimated as 0.477 (0.100) (mean (SD)) days, which maximally increased 2.01-to 2.64-fold higher than the initial steady-state residence time 5.95 (0.899) days post-phlebotomy (P < 0.01). On average, the residence time returned to steady-state values 15.4 (2.36) days post-phlebotomy, which was not significantly different from the initial steady-state value (P > 0.05). The baseline hemoglobin production rate was estimated at 0.0929 (0.0472) g/kg/day and the maximum production rate under stress phlebotomy was estimated at 0.504 (0.0422) g/kg/day. These data indicate that endogenously released Epo under acute anemic conditions can increase hemoglobin production approximately 5-fold. The determined increase in reticulocyte residence time produced under stress erythropoiesis is similar to the commonly reported 2-to 3-fold increase observed in human patients.

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“…Moreover, an elevation in IRF may be the first sign of hematologic recovery in the majority of patients receiving chemotherapy or of engraftment in those that have undergone bone marrow transplantation [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Erroneously elevated immature reticulocyte counts in leukemic patients determined using a Sysmex XE-2100 hematology analyzer

2007

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The immature reticulocyte fraction (IRF) in peripheral blood, as determined by automated reticulocyte analysis, is calculated using the sum of medium and highly fluorescent reticulocyte numbers and provides information about erythropoietic activity in bone marrow. The purpose of this study was to investigate erroneously elevated IRF in leukemic patients, as determined using a Sysmex XE-2100 hematology analyzer (Sysmex, Kobe, Japan). Normal reticulocyte scattergram patterns show regions corresponding to reticulocytes located between matured RBCs and an upper particle (UPP) region, which show a continuum of nonseparated fraction. The UPP represents erythroblasts and some immature reticulocytes. As a control group, peripheral blood was taken from patients with benign hematologic diseases, and their reticulocyte scattergrams all showed a normal pattern; UPP values were all less than 100. However, the reticulocyte scattergrams of 5 of 11 leukemia patients showed abnormal patterns and displayed a gap between RBC and reticulocyte regions. Three patients showed a flag with a message such as "RET Abn Scattergram". IRF results were elevated in these five patients, and their UPP values were above 100. For the remaining six leukemia patients with a normal reticulocyte scattergram pattern, immature reticulocytes were not markedly increased, and UPP values were less than 100. The findings of the present study demonstrate that IRF results may be erroneously elevated in leukemia patients and indicate that hematologists should examine reticulocyte scattergrams and UPP values carefully.

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Immature reticulocytes as an early predictor of engraftment in autologous and allogeneic bone marrow transplantation

Cited by 38 publications

References 20 publications

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients

Pharmacodynamic analysis of time-variant cellular disposition: reticulocyte disposition changes in phlebotomized sheep

Erroneously elevated immature reticulocyte counts in leukemic patients determined using a Sysmex XE-2100 hematology analyzer

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