Track topics on Twitter Track topics that are important to you
Allogeneic stem cell transplantation, the only known curative modality for CML, was abandoned in recent years for a very effective and much less toxic targeted therapy with the tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including stem cell transplantation. The study protocol comprised a cohort of consecutive patients with CML who received allogeneic stem cell transplantation using partial T cell depletion, with no post-transplant GvHD prophylaxis. Forty consecutive patients with CML underwent allogeneic stem cell transplantation from a matched sibling using partial T cell depletion (TCD), in a single institution. Escalated dose of donor lymphocyte infusion (DLI) was given in case of either relapse or presence of minimal residual disease (MRD) as detected by cytogenetic or molecular analysis.
The purpose of the study is to decrease transplant-related toxicity.
Patients were conditioned with oral busulfan 12mg/kg (days -6 to -4), cyclophosphamide 120mg/kg (days -3,-2), rabbit antithymocytic globulin, (Fresenius, Bad Hamburg, Germany) 25mg/kg (days -5 to -1) and fludarabine 200 mg/kg (days -7 to-3). Final busulfan dose was individually determined based on measurements of serum busulfan levels with a target dose of 850-1400 microM x minute.
Transplants were performed in reverse isolation rooms equipped with high-efficiency particulate air filtration systems (HEPA). No post-transplant GvHD prophylaxis was given. Post-transplant infection prophylaxis consisted of acyclovir, itraconazole, trimethoprim-sulfamethoxazole and penicillin VK. Cytomegalovirus (CMV) status was determined weekly using PCR for CMV-DNA and pp65 antigenemia in blood leukocytes, followed by preemptive ganciclovir administration when positive.
Donors Donors were human leukocyte antigen (HLA) A,B,C serologically matched and DR and DQ molecularly matched siblings. Donor stem cells were collected following mobilization with 10 µg/kg/day G-CSF, given subcutaneously for 5 consecutive days. CD34 cells were positively selected using anti-CD34 antibody conjugated to iron-dextran microbeads using CliniMACS device (Miltenyi Biotech, Bergisch Gladbach, Germany) with an aim to collect > 5.0 x 106 CD34 cells/kg.
Disease monitoring Following transplant, all patients were under close surveillance for the presence of minimal residual disease (MRD) using cytogenetic analysis and PCR for the detection of BCR/ABL transcripts. Bone marrow and peripheral blood samples were examined every 3 months in the first year post transplant and every 3-6 months in the subsequent years.
PCR method: RQ-PCR was performed according to the Europe Against Cancer (EAC) protocol.19 The BCR-ABL and ABL copy numbers were calculated by comparing with the standard curve generated using IPSOGEN FusionQuant Standards. The results of quantifying BCR-ABL transcripts were expressed as percentage ratios relative to total ABL transcripts.
A minimum number of 1x104 copies of ABL is the lower limit below which a negative RT-PCR was considered unreliable. In the molecular biology laboratory of the Rambam Health Care Campus the sensitivity for quantitative Q-PCR is (10-5).
Donor leukocyte infusion (DLI). DLI was administered in escalating dose regimen starting from 3 x 106 cells/kg followed as necessary by 1 x 107 cells/kg, 5 x 107 cells/kg and 1 x 108 cells/kg.
DLI was used in case of persistence/reappearance of BCR-ABL transcripts starting from 6 months post transplant onward. In instances where more than 1 DLI was administered the successive escalated dose was given at ≥ 3-month intervals as dictated by MRD follow-up.
Allocation: Non-Randomized, Control: Historical Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Philadelphia Chromosome-positive Chronic Myelocytic Leukemia
Stem cell transplantation
Rambam Health Care Campus
Active, not recruiting
Rambam Health Care Campus
Published on BioPortfolio: 2014-08-27T03:19:44-0400
RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving imatinib mesylate after a donor stem cell transplant may pre...
In this single-center, open-label, no control,prospective clinical trial, a total of 30 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients will be enrolled. Da...
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early first complete remission improves the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic le...
The purpose of this study is to prospectively validate the new risk model, based on minimal residual disease (MRD) response level and oncogenetic status by comparing historical results of ...
This study will evaluate MK0457 in combination with Dasatinib in patients with Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Efficacy and ...
Allogeneic hematopoietic stem cell transplantation, especially haploidentical HSCT, may improve long-term survival for high-risk pediatric patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era.
The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly haploidentical (haplo)-HSCT, in pediatric patients with Philadelphia chromosome-positive acute lymphoblastic le...
Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organiz...
Cytogenetic abnormalities are well-known and powerful independent prognostic factor for various hematological disorders. Although the combination of chemotherapy with tyrosine kinase inhibitor (TKI) i...
Philadelphia chromosome positive acute myeloid leukemia (Ph+ AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. ...
Chronic myelogenous leukemia presenting with central nervous system infiltration, successfully treated with central nervous system-directed chemotherapy followed by allogeneic stem cell transplantation.
With the introduction of tyrosine kinase inhibitors (TKIs), prognosis of chronic myelogenous leukemia (CML) has improved dramatically. However, treatment for blast phase (BP) CML remains a challenge. ...
An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).
Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...