1st BMT – Liam’s Chimerism Engraftment Results

Liam received reduced intensity conditioning with Treosulfan and Fludarabine (research Protocol 2256) regimen A.

DAY+ 432 – 07/18/2012        DNA Chimerism Analysis – Blood

 Derived & naive young  T cells       47%

(CD3+) T Cell                       45% donor origin (55% host)

(CD33+) Myeloid Cells           4% donor origin (96% host)

(CD56+) NK Cells               10% donor origin (90% host)

(CD19+) B Cells                       3% donor origin (97% host)

DAY+ 403 – 06/19/2012        DNA Chimerism Analysis – Blood

Derived & naive young  T cells       52%

(CD3+) T Cell                       47% donor origin (53% host)

(CD33+) Myeloid Cells           2% donor origin (98% host)

(CD56+) NK Cells               10% donor origin (90% host)

(CD19+) B Cells                       2% donor origin (98% host)

DAY+ 367 – 05/14/2012        DNA Chimerism Analysis – Blood

Derived & naive young  T cells       53%

(CD3+) T Cell                       50% donor origin (50% host)

(CD33+) Myeloid Cells           4% donor origin (96% host)

(CD56+) NK Cells               14% donor origin (86% host)

(CD19+) B Cells                       5% donor origin (95% host)

DAY+ 341 – 04/2012        DNA Chimerism Analysis – Blood

T-Cell 60% NK Function 10% B-cell 2% they are running another blood test to look closer at the T-cells if that is low then Liam will need a DLI donor boost which would require more blood from Hunter. We should know more on the new tests tomorrow or next week.

Update: Now things r really getting confusing dr left a message that Liam is producing 56% new cells of hunter so he might not need a DLI yet

(CD3+) T Cell                       60% donor origin (40% host)

(CD33+) Myeloid Cells           unknown% donor origin (unknown% host)

(CD56+) NK Cells               10% donor origin (90% host)

(CD19+) B Cells                        2% donor origin (98% host)

04/26/12               DC45RA/CD31 T-cells                   56% donor (44% host)

DAY+ 243 – 01/10/12        DNA Chimerism Analysis – Blood

(CD3+) T Cell                       72% donor origin (28% host)

(CD33+) Myeloid Cells           12% donor origin (88% host)

(CD56+) NK Cells               35% donor origin (65% host)

(CD19+) B Cells                        11% donor origin (89% host)

DAY+ 200 – 11/29/11        DNA Chimerism Analysis – Blood

(CD3+) T Cell                       76% donor origin (24% host)

(CD33+) Myeloid Cells           10% donor origin (90% host)

(CD56+) NK Cells               40% donor origin (60% host)

(CD19+) B Cells                        8% donor origin (92% host)

DAY+ 138 – 09/27/11        DNA Chimerism Analysis – Blood

(CD3+) T Cell                       62% donor origin (38% host)

(CD33+) Myeloid Cells           23% donor origin (77% host)

(CD56+) NK Cells               71% donor origin (29% host)

(CD19+) B Cells                      22% donor origin (78% host)

DAY +80 – 08/05/11        DNA Chimerism Analysis – BMA

(CD3+) T Cell                       62% donor origin (38% host)

(CD33+) Myeloid Cells           54% donor origin (46% host)

(CD56+) NK Cells               89% donor origin (11% host)

(CD19+) B Cells                      57% donor origin (43% host)

DAY +28 – 06/14/11        DNA Chimerism Analysis

(CD3+) T Cell                       59% donor origin (41% host)

(CD33+) Myeloid Cells           100% donor origin (0% host)

(CD56+) NK Cells               100% donor origin (0% host)

(CD19+) B Cells                      100% donor origin (0% host)

The Nuts and Bolts of Bone Marrow Transplants

http://www.cumc.columbia.edu/dept/medicine/bonemarrow/bmtinfo.html

Bone marrow transplantation (BMT) is a relatively new medical procedure being used to treat diseases once thought incurable. Since its first successful use in 1968, BMTs have been used to treat patients diagnosed with leukemia, aplastic anemia, lymphomas such as Hodgkin’s disease, multiple myeloma, immune deficiency disorders and some solid tumors such as breast and ovarian cancer.

In 1991, more than 7,500 people underwent BMTs nationwide. Although BMTs now save thousands of lives each year, 70 percent of those needing a BMT using donor marrow are unable to have one because a suitable bone marrow donor cannot be found.

http://bloodjournal.hematologylibrary.org/content/116/26/5824.full.pdf

[PDF] Reduced-intensity conditioning significantly improves - Blood

bloodjournal.hematologylibrary.org/content/116/26/5824.full.pdf
File Format: PDF/Adobe Acrobat - Quick View
by RA Marsh - 2010 - Cited by 21 - Related articles
(Blood2010;116(26):5824-5831). Introduction. Familial hemophagocytic lymphohistiocytosis (FHLH) is a collec- tion of primary immune deficiencies

Full Text (PDF) - Blood

bloodjournal.hematologylibrary.org/content/116/…/5824.full.pdf+ht…

by RA Marsh - 2010 - Cited by 21 - Related articles
Published online before print September 20, 2010, doi: 10.1182/blood-2010-04-282392 Blood December 23, 2010 vol.116 no. 26 5824-5831. Show PDF in full

Chimerism analysis is important for monitoring post-transplant outcome and for determining appropriate therapy after transplantation. Since it is the basis for providing early treatment decisions, chimerism analysis requires sensitive and reliable techniques to detect the presence of donor leukocytes in the hosts’ peripheral blood or bone marrow. As lymphoid and myeloid engraftment is asynchronous, lineage-specific chimerism analysis is necessary. This requires the specific enrichment of myeloid and lymphoid cells prior to performing chimerism analysis (e.g. by PCR-based detection of donor- or recipient-specific mini-satellite DNA sequences). http://www.stemcell.com/en/Products/Area-of-Interest/Chimerism.aspx

Chimerism in nonmalignant diseases

http://www.nature.com/bmt/journal/v35/n2/full/1704715a.html

Allogeneic stem cell transplantation is the only curative treatment option for many patients with inherited or acquired nonmalignant diseases as thalassemia, sickle cell disease, immunodeficiency diseases, osteopetrosis, storage diseases, severe aplastic anemia, bone marrow failure syndromes and others (for a review, see Section IV in Thomas et al34). The aim of the procedure in these diseases is to achieve sustained engraftment to (i) improve the hematopoietic function, to (ii) correct the immune competence and/or to (iii) increase or normalize the respective enzyme shortage. Therefore a priori, it is not necessary to replace the recipient hematopoietic system completely. The implementation of a state of mixed chimerism is mostly sufficient to substantially improve the patient’s well being. Thus, to reduce toxic side effects, most conditioning regimens are less myeloablative and thereby mixed chimerism is more likely.60,61,62,63 As a consequence, graft rejection or nonengraftment remained the major causes of treatment failures in this diseases. Sensitization to minor histocompatibility antigens by prior blood product transfusion might increase this danger. The rapid development of complete chimerism in NK and T cells seems to play an important role in achieving sustained engraftment especially in patients who were treated with a dose reduced conditioning regimen.64,65,66,67

http://www.nature.com/bmt/journal/v35/n2/fig_tab/1704715t1.html#figure-title

 

Pediatric Transplants

Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders

http://www.nature.com/bmt/journal/v42/n2/full/bmt200889a.html

http://www.nature.com/bmt/journal/v42/n2/pdf/bmt200889a.pdf

How and when should we monitor chimerism after allogeneic stem cell transplantation?

How and when should we monitor chimerism after allogeneic stem cell transplantation?

P Bader, D Niethammer, A Willasch, H Kreyenberg and T Klingebiel

Source: http://www.nature.com/bmt/journal/v35/n2/full/1704715a.html

Table 1. Chimerism, definition and implications

http://www.nature.com/bmt/journal/v35/n2/fig_tab/1704715t1.html#figure-title

Next table | Figure and tables index

Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation.

source: http://www.bioportfolio.com/resources/pmarticle/93809/Reduced-intensity-Conditioning-Significantly-Improves-Survival-Of-Patients-With-Hemophagocytic-Lymphohistiocytosis-Undergoing.html

Summary

Recent experience suggests that reduced-intensity conditioning (RIC) regimens can improve the outcomes of patients with hemophagocytic lymphohistiocytosis (HLH) undergoing allogeneic hematopoietic cell transplantation (HCT). However, studies directly comparing RIC to myeloablative conditioning (MAC) regimens are lacking. Forty patients with HLH underwent allogeneic HCT between 2003-2009 at Cincinnati Children’s Hospital. Fourteen patients received MAC consisting of busulfan, cyclophosphamide, and anti-thymocyte globulin +/- etoposide. Twenty-six patients received RIC consisting of fludarabine, melphalan, and alemtuzumab. All patients engrafted. Acute GVHD grades II-III occurred in 14% of MAC patients and 8% of RIC patients (p=0.3171). Post-transplant mixed donor/recipient chimerism developed in 18% of MAC patients and 65% of RIC patients (p=0.0110). The majority of patients with mixed chimerism received intervention with reduction of immune suppression +/- donor lymphocyte infusion (DLI) or stem cell boost which stabilized or increased donor contribution to hematopoiesis and prevented relapse of HLH in all but 1 patient. Grade II-III GVHD occurred in 5/14 RIC patients following DLI. The overall estimated 3-year-survival post-HCT was 43% (confidence interval (CI) = +/-26%) for MAC patients and 92% (CI = +/-11%) for RIC patients (p=0.0001). We conclude that RIC significantly improves the outcome of patients with HLH undergoing allogeneic HCT.

Affiliation

Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States;

Journal Details

Name: Blood
ISSN: 1528-0020
Pages:

Links

MESH Definitions

Transplantation Conditioning

Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.

Conditioning, Eyelid

Reflex closure of the eyelid occurring as a result of classical conditioning.

Physical Conditioning, Animal

Physical conditioning of domestic, laboratory, and zoo animals. Includes exercising of animals.

Graft Survival

The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.

Early Diagnosis

Methods to determine in patients the nature of a disease or disorder at its early stage of progression. Generally, early diagnosis improves PROGNOSIS and TREATMENT OUTCOME.

Reduced-intensity conditioning significantly improves survival of 

www.bioportfolio.com › Latest PubMed Articles › Blood

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Treatment of refractory acute GVHD with third-party MSC expanded 

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