child saves mother :)

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child saves mother :)
« on: April 27, 2011, 05:27:37 PM »
i read that in Haploidentical Transplant the child's stem cells save the mother


Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases
This study is ongoing, but not recruiting participants.


First Received on April 14, 2011.   Last Updated on April 15, 2011   History of Changes
Sponsor:  Northside Hospital, Inc. 
Collaborator:  Blood and Marrow Transplant Group of Georgia
 
Information provided by:  Northside Hospital, Inc.
ClinicalTrials.gov Identifier:  NCT01336712

  Purpose
In this study, patients will receive a myeloablative preparative regimen consisting of fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All patients will receive post-transplant Cy in addition to standard post transplant immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially identical to the prior study, with the exception of the substitution of TBI for Busulfan. The investigators hypothesize that this change will significantly reduce the risk of HC, while maintaining the efficacy of the transplant.



Condition  Intervention  Phase 
Chronic Leukemia
Acute Leukemia
Hodgkin's Disease
Non-Hodgkin's Lymphoma
Myelodysplastic Syndrome
 Procedure: Peripheral Blood Stem Cell Transplant
 Phase II
 


Study Type: Interventional 
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Total Body Irradiation-Based Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies


Resource links provided by NLM:


MedlinePlus related topics: Cancer Hodgkin Disease Leukemia Lymphoma Myelodysplastic Syndromes
Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate
U.S. FDA Resources



Further study details as provided by Northside Hospital, Inc.:


Primary Outcome Measures:
Number of patients experiencing hemorrhagic cystitis post transplant [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
1.1 To estimate the incidence of hemorrhagic cystitis following a TBI-based myeloablative haploidentical HSCT in patients with high risk hematologic malignancies. For this study, HC will be defined as the development of late-onset (post-engraftment) macroscopic hematuria and dysuria, associated with positive urine PCR for BK virus or adenovirus. Asymptomatic viruria, with or without microscopic hematuria, will not be considered an episode of HC.




Secondary Outcome Measures:
Survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To obtain estimates of overall survival (OS), event-free survival (EFS), relapse, non-relapse mortality (NRM), engraftment, acute and chronic graft-versus-host disease (GVHD).


Toxicity measurement [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
Characterize additional hematologic and non-hematologic toxicities of TBI-based myeloablative haploidentical HSCT.


Percentage of donor chimerism post-transplant [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
Characterize donor hematopoietic chimerism in peripheral blood at days ~30, ~60, and ~90 after HSCT.



Estimated Enrollment: 18
Study Start Date: April 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Intervention Details:
Procedure: Peripheral Blood Stem Cell Transplant
Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1.

Fludarabine 30 mg/m2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4

Other Names:
TBI
Fludara
Cytoxan
Detailed Description:
Historically, haploidentical HSCT has been associated with significant risks of graft rejection and severe graft versus host disease (GVHD), leading to high treatment related mortality and poor outcomes. The risk of engraftment failure and GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Recently, investigators from Johns Hopkins University demonstrated a new approach to haploidentical transplantation, utilizing a nonmyeloablative preparative regimen, followed by a T cell-replete bone marrow infusion and post-transplantation immunosuppression with high dose Cyclophosphamide (Cy), tacrolimus, and MMF. Clinical studies have shown this approach to be safe and effective with a low incidence of graft rejection, GVHD, and treatment-related mortality. Relapse represents the major cause of treatment failure in these patients, particularly with high-risk myeloid malignancies.

In order to decrease this relapse risk in high-risk patients, the investigators initiated a myeloablative haploidentical HSCT study in January 2009 utilizing Busulfan-based conditioning, post-transplant Cy, and PBSC, instead of BM, as the stem cell source. Outcomes of the 15 patients transplanted to date have been promising with 100% engraftment, low rates of treatment-related mortality, relapse and GVHD, and excellent survival rates. An unexpected outcome of the study was a higher-than-expected rate of BK virus-induced hemorrhagic cystitis (HC) occurring in 7 of 14 evaluable patients. Although there were no deaths attributable to HC, it was associated with significant morbidity in some patients.

HC is a recognized complication of allogeneic transplant therapy. Late onset HC, occurring after engraftment, is due almost exclusively to reactivation of the polyoma BK virus (BKV). Other important risk factors associated with HC include Busulfan-based conditioning, acute GVHD, HLA mismatched transplants, and use of bone marrow as the stem cell source. TBI-based conditioning, prior to myeloablative allogeneic transplant, has been associated with significantly less HC than Busulfan-based conditioning in both retrospective and prospective randomized trials.

Eighteen patients will be accrued to this study. The primary end point of this study is the incidence of HC. The investigators will also examine the incidence of acute and chronic GVHD, engraftment, degree of donor-host chimerism, transplant related morbidity and mortality, as well as disease-free and overall survival. Stopping rules will minimize the risk of untoward or unexpected side effects.

  Eligibility


Ages Eligible for Study:    18 Years to 60 Years
Genders Eligible for Study:    Both
Accepts Healthy Volunteers:    No

Criteria
Inclusion Criteria:

No available matched related or unrelated donor OR a matched related or unrelated donor that is unavailable in the time frame necessary
Availability of a 3/6 or 5/6 matched (HLA-A, B, DR) related donor
Donor must have a negative HLA cross-match in the host vs. graft direction
Donor must be willing to donate mobilized peripheral blood stem cells
Age 18 to </=60 years
Karnofsky Status >/= 70%
Must have one of the following high-risk malignancies
Chronic Myelogenous Leukemia (CML) in chronic phase, resistant and/or intolerant to TKI
CML in accelerated phase
CML blast crisis that has entered into 2nd Chronic phase following induction
Acute Myelogenous Leukemia (AML) in 2nd or subsequent complete remission (CR)
AML primary induction failure but subsequently in CR
AML in 1st CR with poor risk cytogenetics or arising from preceding hematologic disease
AML with marrow blasts <5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH
Myelodysplastic Syndrome (MDS) that is treatment related
MDS that has monosomy 7 or complex cytogenetics
MDS with IPSS score of 1.5 or greater
Chronic myelomonocytic leukemia (CMML)
Acute Lymphocytic Leukemia/lymphoblastic lymphoma (ALL) in 2nd or subsequent complete remission (CR)
ALL with poor-risk karyotype [t(9;22) or bcr-abl fusion, t(4;11) or other MLL translocation] and in 1st CR
ALL with marrow blasts < 5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH
Chronic Lymphocytic Leukemia (CLL)/Prolymphocytic Leukemia (PLL) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
Advance Myelofibrosis, Primary or Post-Polycythemia Vera/Essential Thrombocythemia. Patients must have one of more of the following accelerate phase features, which have been associated with a median overall survival of </= 15 months
Blood or bone marrow blasts >/= 10%
Platelets < 50 x 10*9/L
Chromosome 17 aberrations
Exclusion Criteria:

Patients will not be excluded on the basis of sex, racial or ethnic background
Poor cardiac function: Left ventricular ejection fraction < 45%
Poor pulmonary function: FEV1 and FVD < 60% predicted
Poor liver function: bilirubin >/= 2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT > 3x ULN
Poor renal function: Creatinine >/= 2.0 mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140-age (yrs) x smaller of actual weight vs ideal body weight (kg)/72 x serum creatinine (mg/dl)
HIV positive
Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up.
Prior irradiation therapy rendering patient ineligible for TBI

Re: child saves mother :)
« Reply #1 on: April 27, 2011, 05:34:39 PM »
Baby to cure thalassaemic mom?
Date: 02. 2009
Source: The Times of Inda
19 Feb 2009, 0609 hrs IST, Pinaki Das, TNN
When 24-year-old thalassaemia patient Pinky Barman sought to get pregnant last year, her parents squirmed. Her doctor wasn't sure if she could carry it through and husband Abinash, a non-thalassaemic, thought she was being too ambitious. On Wednesday morning, she gave birth to a boy after months of treatment and medical supervision during which she received at least 15 transfusions.

The newborn has not only brought smiles back to the Barman household but could also cure his mother of the potentially life-threatening ailment. Stem cells taken from cord blood are being used to treat Pinky's thalassaemia, which, doctors said, has never happened anywhere in the world.

"This is the first time a mother's thalassaemia is being treated with stem cells taken from her child's umbilical cord
. There are three instances of mothers being treated but they had other haematological diseases. In India, youngsters have received stem cells from siblings but not the mother," said Prasanta Chaudhuri, a thalassaemia expert who has been treating Pinky for the last 14 years.

A resident of Katwa in Burdwan, Pinky had married Abinash, a small-time businessman, in April 2007. Abinash had volunteered to marry the e-beta thalassaemia patient in response to an ad by her parents - both thalassaemia carriers. Though she needed a transfusion, Pinky's condition had improved since 2006. There were fewer transfusions and she was deemed fit for a normal conjugal life.

In early 2008, Pinky visited Chaudhuri and asked if she could get pregnant. "Generally, thalassaemia patients shy away from pregnancy. They fear the child could be born with the disease. Since Pinky was eager to become a mother and her condition had improved, I gave her the green light. She had to receive several transfusions but she carried it through remarkably well. Now, the stem cells could cure her disease," said Chaudhuri.

Soon after the Caesarean delivery at a nursing home in Howrah, the cord blood was stored at a bank in Joka. Termed haploidentical transplant (transfusion of cord blood stem cells from child to mother), the procedure will take six months. "We plan to begin in two months. If all goes well, she could be cured," said Netaji Subhas Chandra Bose Cancer Research
Institute director Ashish Mukherjee, who will supervise the stem cell transplant.

The case has sent out a strong message. "This proves that thalassaemic women can marry and lead a normal conjugal life. What's more, giving birth could also cure them," said Chauduri.

http://www.healthcord.com/articles.php?id=26583

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Offline Dori

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Re: child saves mother :)
« Reply #2 on: April 29, 2011, 04:55:36 PM »
Hi, I do not understand the importance of the first scientific article, could you tell me?
As the latter, it has been posted before on the forums.

Re: child saves mother :)
« Reply #3 on: April 29, 2011, 07:23:52 PM »
Allogeneic bone marrow (BM) and peripheral blood stem cell (PBSC) transplantation
have become the standard of care for selected patients with acute leukaemia (Gratwohl et
al, 2003). However, many patients are precluded from this potentially curative approach
because of a lack of suitably HLA matched related or unrelated donors (Confer, 1997) or
as a result of the time required to obtain unrelated donor cells (Dini et al, 2003). These
limitations have prompted the search for alternative sources of haemopoietic stem cells
(HSC). Over the last 15 years, transplantation of HSC from haplo-identical family
members has emerged as a viable alternative approach in children with high risk acute
leukaemia (Klingebiel et al, 2004;Veys et al, 2003).Critical procedural developments,
including substantial T cell depletion of the graft to prevent severe graft versus host
disease, escalating stem cell dose to overcome the barrier to engraftment and
improvements in supportive care have established this as an acceptable approach for
selected high-risk patients (Klingebiel et al, 2004;Veys et al, 2003).

dori, i just wanted to show the status of haploidentical transplants becuase the mother being saved by her child is getting this transplant.


 

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