scholarly journals Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2425-2428 ◽  
Author(s):  
AM Yeager ◽  
JE Jr Wagner ◽  
ML Graham ◽  
RJ Jones ◽  
GW Santos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Bone Marrow Transplantation ◽  
Young Children ◽  
Marrow Transplantation ◽  
Antineoplastic Agent ◽  
Area Under The Curve ◽  
Therapeutic Effects ◽  
Older Children ◽  
The Mean

Abstract Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno-occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects.

scholarly journals Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2425-2428 ◽  
Author(s):  
AM Yeager ◽  
JE Jr Wagner ◽  
ML Graham ◽  
RJ Jones ◽  
GW Santos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Bone Marrow Transplantation ◽  
Young Children ◽  
Marrow Transplantation ◽  
Antineoplastic Agent ◽  
Area Under The Curve ◽  
Therapeutic Effects ◽  
Older Children ◽  
The Mean

Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno-occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects.

Secondarily enlarged thymus gland in young children and their examination

1986 ◽  
Vol 67 (2) ◽  
pp. 124-126
Author(s):  
K. E. Krasnoperova
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Young Children ◽  
Replacement Therapy ◽  
Marrow Transplantation ◽  
Genetic Variant ◽  
Primary Immunodeficiencies ◽  
Thymus Gland ◽  
Thymus Transplantation ◽  
Immune Defect

A genetic variant of immunodeficiency with a large thymus is now known, but the proportion of primary immunodeficiencies is small. Such immunodeficiency variants determine the physician's tactics for correction of a specific immune defect, usually using replacement therapy (by bone marrow transplantation, thymus transplantation, or injection of its hormones).

Preemptive Bone Marrow Transplantation and Event-Free Survival in Fanconi Anemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3624-3624
Author(s):  
Nicholas Economou Khan ◽  
Philip S. Rosenberg ◽  
Blanche P. Alter
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Fanconi Anemia ◽  
Marrow Transplantation ◽  
Standard Care ◽  
Bone Marrow Failure ◽  
Event Free Survival ◽  
Free Survival ◽  
Increased Risk ◽  
The Mean

Abstract Background: Fanconi anemia (FA) is a primarily autosomal recessive bone marrow failure and cancer predisposition syndrome associated with mutations in the FA/BRCA DNA damage response pathway. The median age at diagnosis of FA is 7 years; the diagnosis is often made due to recognition of characteristic birth defects. Over half of patients with FA develop severe bone marrow failure (BMF) by age 50 years, one in ten develop acute myeloid leukemia (AML), and one in four develop a solid tumor (ST) as their first event. Successful allogeneic bone marrow transplantation (BMT) is potentially curative of FA's hematologic manifestations but introduces risks of transplant-related mortality (TRM) and morbidity. We hypothesized that preemptive bone marrow transplantation (PE-BMT) for individuals diagnosed prior to the development of BMF, AML, or ST, would increase event-free survival (EFS) if the risks associated with transplantation were sufficiently low. Methods: We developed a mathematical decision model (Markov) of EFS with the assumption that successful PE-BMT would eliminate the risks of BMF and AML, but would introduce a procedural risk of TRM. We modeled the EFS of PE-BMT at variable ages at decision ranging from birth to 30 years, and without and with an increase in the rate of ST following BMT above the level in untransplanted patients with FA. We developed our model using empirical estimates of the age-specific conditional probabilities of BMF, AML, and ST (Alter et al, BJH, 2010), and a 4.4-fold estimated increased risk of ST following BMT (Rosenberg et al, Blood, 2005). We tested the sensitivity of the model over a range of values for TRM and an increased risk of ST following BMT, and evaluated the model using TreeAge Pro 2014 (TreeAge Software, Inc, Williamstown MA, http://www.treeage.com). Results: Children diagnosed at age 7 years receiving standard care could expect to live an additional 16 years before experiencing BMF, ST, or AML, and thus survive free of an event until an average age of 23 years. If those children instead received PE-BMT with a 10% risk of TRM, they could expect to survive an additional 29 years and be cancer-free until an average age of 36 years. However, if PE-BMT were to increase the rate of ST 4.4-fold, PE-BMT would only increase the mean EFS by 2 years over standard care, until an average age of 25 years. PE-BMT would increase the mean EFS at all ages if TRM was ≤10% and the risk of ST was the same as in untransplanted patients. PE-BMT would decrease the mean EFS when performed after age 9 years if there was 10% TRM and a 4.4-fold increased rate of ST. PE-BMT at age 18 years with 10% TRM would increase the mean EFS if it did not affect the trajectory to ST, but would decrease the mean EFS if it modestly increased the rate of ST (≥2.2-fold). Conclusions: PE-BMT in patients with FA may provide an event-free survival benefit so long as the risk of TRM appears to be low (≤10%) and the regimen has little or no impact on the development of ST. The decision was particularly sensitive to the increase in ST following BMT. Our model suggests that older ages at decision, higher risks of TRM, and greater relative risks of ST following transplant would lead to PE-BMT being a less desirable strategy. Our estimates of event-free survival may be used to inform shared decision making between providers and families, with attention paid to patient values and the morbidity associated with BMT. Disclosures No relevant conflicts of interest to declare.

Augmented Proliferation of Human Alveolar Macrophages After Allogeneic Bone Marrow Transplantation

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 667-673 ◽  
Author(s):  
Koh Nakata ◽  
Hajime Gotoh ◽  
Junichi Watanabe ◽  
Takeshi Uetake ◽  
Iwao Komuro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Alveolar Macrophages ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Mononuclear Phagocytes ◽  
Allogeneic Bone ◽  
The Mean

After allogeneic bone marrow transplantation (allo-BMT), recipient alveolar macrophages (AM) are gradually replaced by AM of the donor origin. An influx of mononuclear phagocytes of donor origin to the lung is responsible for the repopulation, but the detailed kinetics remain unclear. We therefore studied 24 BMT recipients who underwent bronchoalveolar lavage (BAL) from 24 to 83 days after BMT. AM cell number, size, morphology, proliferating ability, and genotype of AM were measured. Before day 50, the number and size of AM in BAL fluid were similar to those of normal nonsmokers. However, after day 50, the mean number of AM increased threefold and the mean cell size decreased due to the increase of small AM. These small cells are presumably of donor origin based on DNA fingerprinting analysis and based on fluorescence in situ hybridization for the Y chromosome in a sex-mismatched case. Immunohistochemistry and cell cycle analysis demonstrated that the increase in AM number coincided with a remarkable increase of AM expressing proliferating cell nuclear antigen, suggesting that small AM are proliferating. This is the first report representing that augmented proliferation of donor AM in situ may contribute to the reconstitution of AM population after BMT.

Total body irradiation and bone marrow transplantation for immunodeficiency disorders in young children

1990 ◽  
Vol 18 ◽  
pp. 114-117 ◽  
Author(s):  
F.E. Halberg ◽  
W.M. Wara ◽  
K.E. Weaver ◽  
D.W. Wara ◽  
A.R. Ablin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Young Children ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Total Body

scholarly journals Growth after bone marrow transplantation in young children conditioned with chemotherapy alone

1997 ◽  
Vol 19 (3) ◽  
pp. 253-256 ◽  
Author(s):  
L Adan ◽  
M-L de Lanversin ◽  
C Thalassinos ◽  
J-C Souberbielle ◽  
A Fischer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Young Children ◽  
Marrow Transplantation

Acute heart failure in bone marrow transplantation: Impact of intravenous immune globulin as adjuvant therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16512-16512
Author(s):  
P. Salcedo ◽  
E. Shpall ◽  
W. Yusuf ◽  
S. Roberson ◽  
M. Woods ◽  
...  
Keyword(s):  
Heart Failure ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Heart Failure ◽  
Marrow Transplantation ◽  
Acute Decompensated Heart Failure ◽  
Nyha Class ◽  
Decompensated Heart Failure ◽  
The Mean ◽  
Post Therapy

16512 Background: Little is known regarding management or treatment of cardiac failure after bone marrow transplantation. We investigated the management, treatment and outcome of new onset acute decompensated heart failure (ADHF) after bone marrow transplantation (BMT) with beta blockers, ace-inhibitors and adjuvant intravenous immune globulin (IVIG) therapy. Methods: We retrospectively examined 25 patients with ADHF. Eleven of these patients developed congestive heart failure within 100 days of BMT. Baseline echocardiograms were normal prior to admission and all patients were hospitalized and evaluated for left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class. Patients with acute heart failure were treated with standard heart failure medications and patients post-BMT were treated with standard heart failure therapy plus adjuvant (IVIG) (500mg/Kg/day) for 48 hours. Baseline LVEF and NYHA class of 11 patients pre- and post-BMT were compared with LVEF and NYHA class of 14 patients with ADHF that did not receive a BMT. Results: The baseline diagnosis for all patients in the BMT group was NYHA class 4 and post-therapy improved to class 1.2. The baseline diagnosis for all patients in the non-BMT group were NYHA class 3.7 and improved to class 1.2 with medical therapy. The mean LVEF in the BMT group at diagnosis of ADHF was 27.5% and the mean post-therapy with IVIG was 57.6%. The mean baseline LVEF in the group not undergoing BMT and at diagnosis of ADHF was 28.2% and improved post-therapy to 45.2%. Conclusions: Acute decompensated heart failure in the cancer patient is highly treatable with aggressive medical management. Patients with ADHF after BMT and treated with IVIG may have potential clinical benefits with IVIG and standard medical therapy. Significant improvement in LVEF and NYHA were present in the BMT group versus the non-BMT group. These data suggest that BMT outcomes may be improved with routine heart failure management. Further randomized studies should be conducted. [Table: see text] No significant financial relationships to disclose.

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