scholarly journals 52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439 ◽  
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

Abstract The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

scholarly journals Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia [see comments]

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 277-279 ◽  
Author(s):  
G Socie ◽  
M Henry-Amar ◽  
JM Cosset ◽  
A Devergie ◽  
T Girinsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Malignant Tumors ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Male Patients

Abstract From May 1980 to December 1989, 107 consecutive patients with non- constitutional severe aplastic anemia underwent bone marrow transplantation at our institution using cyclophosphamide and thoraco- abdominal irradiation as conditioning regimen. During the same period, 40 patients with Fanconi anemia were also grafted after a similar conditioning, giving a total series of 147 patients. With a mean follow- up of 64 months, four male patients developed a solid malignant tumor, a number that leads to an 8-year cumulative incidence rate of 22% (eg, relative risk to general population = 41, P less than .001). These results should be considered as a warning to clinicians who follow these successfully grafted long-term patients.

scholarly journals Beneficial effect of angiotensin converter enzyme inhibitors on left ventricular deformation in patients with hematologic malignancies after bone marrow transplantation

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
I Ikonomidis ◽  
K Katogiannis ◽  
M Stamouli ◽  
G Makavos ◽  
A Frogoudaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Ejection Fraction ◽  
Marrow Transplantation ◽  
Longitudinal Strain ◽  
Myocardial Dysfunction ◽  
Global Longitudinal Strain ◽  
Hematologic Malignancies ◽  
Left Ventricular

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Hellenic society of lipidiology, atherosclerosis and cardiovascular disease Background/Introduction:  Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of cardiotoxic treatment. Patients and methods 60 patients age 46,3 ± 12,9 years old, 19 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive 2,5 mg enalapril bid daily or placebo. We measured at baseline, before transplantation, and after three months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) LV Epicardial Strain (GLSepi), iii) LV Endocardial Strain (GLSendo), by speckle tracking imaging, iv) LV End Diastolic ,End Systolic Volume and Ejection Fraction (LVEF). Results   The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with enalapril did not show a deterioration of LV GLS and GLSepi [ p = 0,540 and p = 0,422)], Conversely, patients treated with placebo group, presented a significant impairment of LV GLS and GLSepi [p = 0,041 and p = 0,028)] three months after bone marrow  transplantation. No significant changes were found in LVEF after treatment with enalapril ( p = 0,692) or the placebo ( p = 0,892). Table 1 Conclusions   Treatment with enalapril prevented deterioration of myocardial deformation three months after bone marrow transplantation Table 1 group baseline 3 months follow-up p Longitudinal strain apical 4 chambers view placebo -20.56 ± 2.55 -19.46 ± 2.59 0.154 enalapril -20.41 ± 3.31 -19.70 ± 3.70 0.433 Longitudinal strain apical 2 chambers view placebo -20.5 ± 1.97 -16.11 ± 10.38 0.149 enalapril -20.30 ± 3.90 -20.00 ± 3.82 0.763 Longitudinal strain apical 3 chambers view placebo -19.55 ± 2.36 -18.55 ± 2.43 0.197 enalapril -20.01 ± 4.09 -19.26 ± 3.68 0.489 Global Longitudinal Strain placebo -20.19 ± 1.76 -18.96 ± 2.08 0.041 enalapril -20.24 ± 3.58 -19.66 ± 3.65 0.540 Average Global Epicardial Strain placebo -17.82 ± 1.45 -16.60 ± 1.68 0.028 enalapril -17.84 ± 3.09 -17.16 ± 3.20 0.422 Average Global Endocardial Strain placebo -23.03 ± 2.15 -21.96 ± 2.56 0.181 enalapril -23.07 ± 4.19 -23.60 ± 4.17 0.666 EF (Simpon’s method) placebo 59.46 ± 6.59 59.69 ± 6.79 0.892 enalapril 58.65 ± 7.63 59.45 ± 9.28 0.692 Left ventricular parameters during 3 months of follow-up.

Outcome Of Bone Marrow Transplantation In Lebanese Children With β-Thalassemia Major

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5505-5505
Author(s):  
Adlette Inati ◽  
Javid Gaziev ◽  
Hussein A Abbas ◽  
Serge Korjian ◽  
Yazan Daaboul ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Iron Overload ◽  
Late Effects ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Increased Risk

Abstract Abstract 5505 Introduction Bone marrow transplantation (BMT) represents the only curative modality for β-Thalassemia Major (β–TM). Best results are achieved in regularly transfused and chelated pediatric patients. Outcome of BMT in 36 Lebanese children who received treatment in the Mediterranean Institute of Hematology (IME) centers in Italy is presented. Methods 36 children with β–TM treated at Chronic Care Center, Lebanon underwent BMT from HLA compatible donors in IME centers.  Each was assigned a Pesaro risk category and underwent a percutaneous liver biopsy before BMT. Conditioning regimen consisted of busulfan, cyclophosphamide ± Thiotepa and ATG. GvHD prophylaxis included cyclosporine A, methotrexate and prednisolone. Engraftment was evaluated by fluorescence in situ hybridization. Transplant related mortality (TRM) and other complications were calculated as cumulative incidence. Analyses were performed using R software. Results 36 hepatitis B and C negative children with β –TM (M/F 1:l),  median age 8.5 years, underwent BMT from HLA identical donors. The most common β-globin mutation was homozygous IVS1.110 (39.29%). 20.5%, 55.9% and 23.5% had Pesaro risk class 1, 2 and 3, respectively.  Mean injected CD34+ cells, total nucleated cells and CD3+ cells/recipient  were 10.9x106 /Kg,  8.69x108/Kg and 66.3x106 /Kg. Absolute neutrophil count >0.5 x109 and platelet count >20 x 109 were reached in all patients within a mean of +19.44±4 and +19.15 ±6.5 days. Regular chimerism surveillance  showed complete engraftment in 35/36 children (97.3%)  up till+ 4.2 years median follow up. 1/36 (2.7%) had partial engraftment but continued to be transfusion independent with a mean Hb of 9g/dcl for +1155 days. Immune reconstitution was seen in all patients by + 12 -18 months. At a median follow up of + 6.20 years, 32/36 (89%) of children are alive and transfusion independent. Among those who died (11%), 1 had multi organ failure, 2 had grade 4 acute GvHD and 1 had fulminant interstitial pneumonitis.  47% had acute GvHD which was not correlated with donor relation, conditioning regimen, and pre-BMT hepatomegaly, splenomegaly and transfusion frequency. 8/36 (22%) had grade 2 to 4 acute GvHD of which 75% resolved on treatment while 25% (all grade 4) were fatal. 9/32 (28%) surviving children had chronic GvHD completely resolved on treatment and not correlated with  any recipient, donor or treatment feature.  Other transplant related complications included CMV reactivation, sepsis, EBV and candida infections, hemorrhagic cystitis, cerebral toxoplasmosis, tuberculosis and transient cyclosporine  related renal and neurotoxicity, all completely resolved on treatment. Late effects of transplant were monitored in 27 children.  Iron overload data utilizing magnetic resonance imaging at + 3.1 year median follow up showed that mean baseline LIC for 27 patients was 11.3 mg Fe/g dw but ranged as high as 36.6 mg Fe/g dw. Median serum ferritin was 1255 ng/mL, with a maximum of 5884 ng/mL.  9/27 (33.3%) children had significant iron overload defined as SF >2500 ng/ml, or LIC >15 mg Fe/g dw, or T2* <20 msec, levels known to be associated with increased risk of progressive organ dysfunction and death. Median ejection fraction was 68 % (range 58-75%). Up till + 6.20 years median follow up,  serum immunoglobulins, alanine and aspartate aminotransferases, BUN, creatinine and creatinine clearance were normal in all 27 children.  Hypothyroidism, growth retardation and diffuse persistent vitiligo were seen in 3/25 (12%), 4/25 (16%) and 1/25 (4%) survivors respectively. Summary Our results reflect an excellent outcome for Lebanese children with β –TM undergoing transplantation. TRM was low and associated complications were transient and manageable. Significant iron overload was, however, noted years after BMT underscoring the need for long term monitoring for iron overload and for iron removal to prevent associated negative outcomes.  This study highlights the need for monitoring for late effects for years after transplant. It also demonstrates the effectiveness of international collaboration in facilitating cure for thalassemia in developing countries as Lebanon. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen.

1989 ◽  
Vol 169 (2) ◽  
pp. 493-502 ◽  
Author(s):  
Y Sharabi ◽  
D H Sachs
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Host Resistance ◽  
Marrow Transplantation ◽  
Whole Body ◽  
Mixed Chimerism ◽  
Skin Grafts ◽  
Preparative Regimen ◽  
Donor Specific Tolerance ◽  
Specific Tolerance

The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia.

scholarly journals Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia [see comments]

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 277-279 ◽  
Author(s):  
G Socie ◽  
M Henry-Amar ◽  
JM Cosset ◽  
A Devergie ◽  
T Girinsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Malignant Tumors ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Male Patients

From May 1980 to December 1989, 107 consecutive patients with non- constitutional severe aplastic anemia underwent bone marrow transplantation at our institution using cyclophosphamide and thoraco- abdominal irradiation as conditioning regimen. During the same period, 40 patients with Fanconi anemia were also grafted after a similar conditioning, giving a total series of 147 patients. With a mean follow- up of 64 months, four male patients developed a solid malignant tumor, a number that leads to an 8-year cumulative incidence rate of 22% (eg, relative risk to general population = 41, P less than .001). These results should be considered as a warning to clinicians who follow these successfully grafted long-term patients.

Comparison of Conditioning Regimens with or without Total Body Irradiation in Bone Marrow Transplantation from an Alternative Donor.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5172-5172 ◽  
Author(s):  
Hiromasa Yabe ◽  
Shunichi Kato ◽  
Miharu Yabe ◽  
Kazuko Kudo ◽  
Hiroshi Yagasaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Alternative Donor ◽  
Conditioning Regimens ◽  
Total Body

Abstract An optimum conditioning regimen is indispensable in improving outcomes for patients with acquired aplastic anemia (AA) who receive bone marrow transplantation (BMT) from an alternative donor. Although high-dose total body irradiation (TBI) is effective in enhancing engraftment, intensive conditioning regimens are associated with increased regimen-related toxicity, which results in a decreased success rate. Currently, two different approaches are primarily used; a conditioning regimen including low-dose TBI and a fludarabin-based regimen without TBI. We attempt to clarify the efficacy and regimen-related toxicity of these two approaches. Ten patients (7 males, 3 females; median age 12y; range 9–17y) underwent an alternative donor transplant following a conditioning regimen with low-dose TBI (TBI group); patients received cyclophosphamide (50 mg/kg/d on days −5 to −2), antithymocyte globulin (Thymoglobulin, 2.5 mg/kg/d on days −5 to −2) and TBI (2.5 Gy x 2 on day −1). The donor was unrelated in 9 patients (3 were serologically HLA A or B antigen mismatched; 3 were serologically HLA DR antigen mismatched, 1 was both serologically and genotypically DR antigen mismatched; 1 was genotypically DRB1 mismatched; 1 was a genotypically complete match) and was a family member in 1 patient (serologically HLA A-mismatched father). Twelve patients (6 males, 6 females; median age, 11 y; range 2–20 y) received a conditioning regimen of fludarabine (25 mg/kg/d on days −5 to −2), cyclophosphamide (750 mg/m 2 /d on days −5 to −2), thymoglobulin (1.5 mg/kg/d on days −5 to −2) and thoracoabdominal irradiation (TAI, 3Gy x 1 on day −1) (TAI group). The donor was unrelated in 11 patients (8 were genotypically complete matches, and 3 were genotypically DRB1 antigen mismatched) and a family member in 1 patient (3 antigen-mismatched mother). The source of stem cells was unmanipulated bone marrow. Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus (0.02 mg/kg from day −1) and short-term methotrexate. Rejection was seen in one patient in each group. The doses of infused nucleated marrow cells were less than 2.0 x 10 8 /kg in both patients, and both patients then received a second transplant and achieved full donor chimerism. Acute GVHD grade II-IV developed in 2/10 evaluable patients in the TBI group and in 3/12 patients in the TAI group. Chronic GVHD developed in 5/9 evaluable patients in TBI group and 3/10 evaluable patients in TAI group. Median follow up was 9 months (4–27 months) in the TBI group and 21 months (3–33 months) in the TAI group. Both conditioning regimens were well tolerated and effective even in HLA-mismatched unrelated donor transplantation. Long-term follow up is warranted in order to compare the late sequelae in both regimens.

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