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Immune recovery after in vivo T-cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta-thalassemia children.

BACKGROUND: The clinical outcome of hematopoietic stem cell transplantation (HSCT) in those with severe beta-thalassemia (β-TM) is closely related to post-transplantation immune reconstitution (IR). However, the data on the IR in these settings are scarce. METHODS: A prospective analysis of the clinical outcome and IR in 47 children with severe β-TM who underwent in vivo T-cell depletion myeloablative conditioning and matched sibling donor HSCT was performed. Immune reconstitution, including immune cell subset counts, as well as the generation of new T and B cells assays after HSCT, was measu

Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The

Incidence and risk factor of hemorrhagic cystitis after allogeneic transplantation with fludarabine, busulfan, and anti-thymocyte globulin myeloablative conditioning.

BACKGROUND: Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown. METHODS: We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall

Does anti-thymocyte globulin have a place in busulfan/fludarabine conditioning for matched related donor hematopoietic stem cell transplantation?

BACKGROUND/AIMS: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. METHODS: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG

Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell transplantation.

There are limited data to guide the choice of high-dose therapy (HDT) regimen before autologous hematopoietic cell transplantation (AHCT) for patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL). We studied 4917 patients (NHL, n = 3905; HL, n = 1012) who underwent AHCT from 1995 to 2008 using the most common HDT platforms: carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) (n = 1730); cyclophosphamide, BCNU, and etoposide (CBV) (n = 1853); busulfan and cyclophosphamide (BuCy) (n = 789); and total body irradiation (TBI)-containing treatment (n = 545). CBV was divided into CBV(h

Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study.

BACKGROUND: We report a prospective multicenter phase II study of haploidentical hematopoietic stem cell transplantation using CD3/CD19-depleted grafts after reduced intensity conditioning with fludarabine, thiotepa, melphalan and OKT-3. DESIGN AND METHODS: Sixty-one adults with a median age of 46 years (range 19-65 years) have been enrolled. Diagnoses were acute myeloid leukemia (n=38), acute lymphoblastic leukemia (n=8), non-Hodgkin's lymphoma (n=6), myeloma (n=4), chronic myeloid leukemia (n=3), chronic lymphatic leukemia (n=1) and myelodysplastic syndrome (n=1). Patients were considered h

Cyclosporine A and reduced-intensity conditioning allogeneic stem cell transplantation for relapsed angioimmunoblastic T cell lymphoma with hemophagocytic syndrome.

No standard therapeutic approaches have so far been established for the treatment of relapsed angioimmunoblastic T-cell lymphoma (AITL), a subtype of non-Hodgkin lymphoma. This case report describes an AITL patient who relapsed with hemophagocytic syndrome (HPS) two months after receiving high-dose chemotherapy (HDCT) supported by autologous peripheral blood stem cell transplantation (PBSCT). The patient was successfully treated with cyclosporine A (CsA) and subsequent allogeneic PBSCT with reduced intensity conditioning regimen (RIST). RIST may deserve consideration for treatment of AITL pati

Alternate donor hematopoietic cell transplantation (HCT) in non-Hodgkin lymphoma using lower intensity conditioning: a report from the CIBMTR.

We analyzed the outcomes of 248 (61% male) adult recipients of HLA-matched unrelated and HLA-mismatched related donor hematopoietic cell transplantation (HCT) for non-Hodgkin lymphoma (NHL) after reduced or lower intensity conditioning (RIC), reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1997 to 2004. Median age was 52 (range: 18-72 years); 31% had a Karnofsky performance score <90. Follicular NHL (43%) was the major histology. Incidence of grades II-IV acute graft-versus-host disease (aGVHD) was 43% at 100 days; and chronic GVHD (cGVHD) was 44% at

Optimizing the conditioning regimen for allogeneic stem-cell transplantation in acute myeloid leukemia; dose intensity is still in need.

Allogeneic stem-cell transplantation (SCT) is potentially curative therapy in AML by providing both dose-intensive chemo-radiotherapy and induction of graft-versus-leukemia (GvL) effect. Historically, more emphasis was given to the intensity of conditioning. Over the last decade the pendulum turned more towards induction of GvL as the primary goal. A plethora of non-myeloablative (NMA) and reduced-intensity conditioning regimens (RIC) were introduced trying to reduce transplant-related toxicities and allow SCT in elderly and medically infirm patients. In addition, reduced-toxicity myeloablativ

Autologous transplantation for relapsed non-Hodgkin's lymphoma using intravenous busulfan and cyclophosphamide as conditioning regimen: a single center experience.

High-dose chemotherapy with autologous SCT has become standard of care for patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). To improve safety and efficacy of this treatment, new conditioning regimens are being developed. We retrospectively reviewed clinical data of patients with relapsed NHL treated at our institution with i.v. BU and CY (BU/CY) as conditioning regimen for autologous SCT between January 2000 and April 2005. We identified 43 patients (24 men, 19 women, median age 50) with diffuse large B-cell lymphoma (n=28), follicular lymphoma (n=8), mantle cell lymphoma (n=4)

Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies.

Toxicity-reduced conditioning is being used for allogeneic stem cell transplantation in older and/or comorbid patients. We report on the treatment of 133 patients (median age: 55.6 years [23-73 years]) with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS; n = 81), myeloproliferative syndromes (MPS; n = 20), and lymphoid malignancies (n = 32) using conditioning with FBM: fludarabine (5 x 30 mg/m(2)), 1,3-bis(2-chloroethyl)-1-nitrosourea (or carmustine, BCNU; 2 x 200 mg/m(2)), and melphalan (140 mg/m(2)). Patients 55 years or older received fludarabine with reduced BCNU (2 x150 mg/m(2

In stem cell transplantation, by limiting the morbidity of graft-versus-host disease tolerance to myeloablative conditioning is improved.

Myeloablative conditioning followed by T-cell depletion of grafts and reduced intensity conditioning (RIC) has both been shown to decrease treatment related mortality (TRM). However in RIC the incidence of graft vs. host disease (GvHD) is high and patients with aggressive diseases tend to relapse. Following myeloablative conditioning, patients with chemotherapy-responsive hematological malignancies underwent transplantation from HLA identical siblings. GvHD prophylaxis was by ex viva T-cell depletion with alemtuzumab. The outcome of these patients was analysed. At transplantation, the median a

Transplantation of allogeneic CD34-selected stem cells after fludarabine-based conditioning regimen for children with mucopolysaccharidosis 1H (M. Hurler).

Hurler syndrome (MPS1H) is a progressive inborn error of mucopolysaccharide metabolism leading to premature death. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and improve long-term survival. However, large studies have shown that preparative regimen-related toxicity (RRT) and graft failure rates have been relatively high. We transplanted five Hurler children with a fludarabine-based conditioning regimen, consisting of fludarabine/busulphan/ATG for matched family donor (MFD), with the addition of melphalan for mismatched family donor and matched unrelated donor

Long-term mixed chimerism after immunologic conditioning and MHC-mismatched stem-cell transplantation is dependent on NK-cell tolerance.

T-cell tolerance is mandatory for major histocompatibility complex (MHC)-mismatched stem-cell transplantation without cytoreduction. Here, we used a cytotoxicity assay based on the infusion of differentially carboxyfluorescein succinimidyl ester (CFSE)-labeled syngeneic and donor splenocytes to determine the survival of donor cells in vivo. In vivo cytotoxicity data showed that treatment with anti-CD40 ligand monoclonal antibody in combination with a low dose of MHC-mismatched bone marrow cells was sufficient to induce T-cell tolerance. However, CFSE-labeled donor cells were still eliminated.

Immunotherapy of cancer by active vaccination: does allogeneic bone marrow transplantation after non-myeloablative conditioning provide a new option?

The critical role of antigen-specific T cells in cancer immunotherapy has been amply demonstrated in many model systems. Though success of clinical trials still remains far behind expectation, the continuous improvement in our understanding of the biology of the immune response will provide the basis of optimized cancer vaccines and allow for new modalities of cancer treatment. This review focuses on the current status of active therapeutic vaccination and future prospects. The latter will mainly be concerned with allogeneic bone marrow cell transplantation after non-myeloablative conditioning

High-dose idarubicin and busulphan as conditioning for autologous stem cell transplantation in acute myeloid leukemia: a feasibility study.

INTRODUCTION: Between 30 and 50% of patients with acute myeloid leukemia still relapse after autologous stem cell transplantation. We investigated the feasibility of a new conditioning regimen consisting of high dose IDA plus oral busulphan in patients undergoing autologous transplantation. MATERIALS AND METHODS: Patients (n = 13) were given three days continuous infusion IDA, followed by four days conventional dose oral busulphan as conditioning. Peripheral blood stem cells were used in all cases. Eleven patients were in CR1. Patients with t(8;21) and inv(16) as well as those with acute prom

Ex vivo expanded allogeneic cord blood progenitor cell transplantation with a non-myeloablative conditioning regimen would cure autoimmune diseases.

Loss of self-tolerance is the basis for autoimmune disease. Autologous as well as allogeneic stem cell transplantation is increasingly being considered and used for therapy of autoimmune disease. Non-myeloablative conditioning has been shown in the context of malignant diseases to be feasible. Cord blood transplantation has been associated with significantly less graft-versus-host disease (GVHD) than other forms of allotransplantation. Ex-vivo expansion of this limited resource is increasingly becoming feasible. It is being hypothesized that ex-vivo expanded cord blood progenitor cell transpla

Allogeneic bone marrow transplantation following busulfan-cyclophosphamide with or without etoposide conditioning regimen for patients with acute lymphoblastic leukaemia.

We have investigated the feasibility and efficacy of administering a radiation-free preparative regimen in the setting of allogeneic bone marrow transplantation (BMT) in 40 consecutive patients with acute lymphoblastic leukaemia (ALL). Busulfan (4 mg/kg/d x 4 d) and cyclophosphamide (50 mg/kg/d x 4 d) (BuCy4) were given in 29 patients and 11 received busulfan (4 mg/kg/d x 4 d), etoposide (60 mg/kg) and cyclophosphamide (60 mg/kg/d x 2 d) (BuCy+VP - 16). Median age was 22 years (range 1-50); 11 patients were children < or = 15 years of age. All children and 20 adults were at high risk of relaps

Снижение дозы по сравнению со стандартными кондиционирования мелфалами для автоматической трансплантации стволовых клеток в множестве миеломы: ретроспективное исследование с одним центром.

Это ретроспективное одноцентральное исследование позволило оценить эффективность и безопасность сокращенного режима кондиционирования мелфала (см.140–180 мг/м2 для аутологической трансплантации стволовых клеток (ASCT) у пациентов с множественной миеломой (MM), не имеющих права на стандартную дозу (ASCT)200 мг/м2. Клинические результаты сравнивались между пациентами, получившими сокращенную дозу, и стандартными дозированными мелфаланами по сравнению с а five- годовой период с предварительным анализом подгрупп в зависимости от возраста и почечной функции. Результаты показали, что, несмотря на ме

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… For patients with normal renal function, the standard pre-transplantation conditioning regimen for ASCT remains melphalan 200 mg/m 2 (Mel200). This dose has demonstrated proven superiority over both 280 mg/m 2 and 100 mg/m 2 dosing regimens [ 8 , 9 ]. …