Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic cell transplant (HCT) recipients. Iron overload increases the risk of infections, ...veno-occlusive disease and hepatic dysfunction post transplant. Elevated pretransplant ferritin levels have been reported to increase the risk of nonrelapse mortality following HCT and might influence the risk of acute and chronic GVHD. Serum ferritin is sensitive but not specific for iron overload and is a poor predictor of body iron burden. Estimation of hepatic iron content with a liver biopsy or magnetic resonance imaging should be considered prior to initiating therapy for post transplant iron overload. A subgroup of transplant survivors with mild iron overload and no end-organ damage may not need therapy. Phlebotomy is the treatment of choice with iron-chelation therapy reserved for patients not eligible for phlebotomy. Natural history, evolution and treatment of iron overload in transplant survivors have not been adequately investigated and more studies are needed to determine its impact on short-term and long-term morbidity and mortality.
The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow ...Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.
The natural history of multiple myeloma (MM) was revolutionized by the introduction of haematopoietic stem cell transplantation to the treatment armamentarium of this disease. Defined subgroups of MM ...patients (such as the elderly or dialysis-dependent) have required an individualized approach in order to minimize the transplant-related mortality. Little, however, is known about the management of 12-30% of MM patients with coexistent AL amyloidosis as the amyloidopathy is often overlooked and when recognized these patients commonly are excluded from clinical trials. While occult amyloidosis appears to have no impact on the toxicity and outcome of MM patients, the presence of symptomatic amyloidopathy clearly worsens their prognosis. Use of induction chemotherapy drugs that can cause further damage to the heart (Adriamycin), nervous system (Vincristine) or kidneys should be avoided as should lengthy delays in proceeding to autograft. Further, refining the transplant eligibility criteria for this subgroup of patients with co-existent amyloidopathy to include the number of organs involved and the degree of cardiac involvement (NYHA class, Troponins and NT-pro-BNP levels) along with melphalan dose-adjustment will minimize the treatment-related toxicity and mortality and possibly allow a reversal of the organ damage induced by the amyloidogenic light chain.
Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors ...approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and -DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2-4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor.
Hematopoietic stem cell transplantation (HSCT) is the definitive cure for many malignant and nonmalignant diseases. However, delays in immune reconstitution (IR) following HSCT significantly limit ...the success of transplantation and increase the risk for infection and disease relapse in the transplant recipient. Therefore, ways to measure and to manipulate immune recovery following HSCT are emerging and their success depends directly upon an enhanced understanding for the underlying mechanisms responsible for reconstituted immunity and hematopoiesis. Recent discoveries in the activation, function, and regulation of dendritic cell (DC), natural killer (NK) cell, and T-lymphocyte subtypes have been critical in developing immunotherapies used to prevent graft-versus-host disease and to enhance graft-versus-leukemia. For example, regulatory T cells that induce tolerance and NK receptor-tumor ligand disparities that result in tumor lysis are being used to minimize GVHD and tumor burden, respectively. Furthermore, expansion and modulation of immune effector cells are being used to augment hematopoietic and immune recovery and to decrease transplant-related toxicity in the transplant recipient. Specifically, DC expansion and incorporation into antitumor and anti-microbial vaccines is fast approaching application into clinical trials. This paper will review our current understanding for IR following HSCT and the novel ways in which to restore immune function and decrease transplant-related toxicity in the transplant recipient.
Umbilical-cord blood from unrelated donors can restore hematopoiesis in adults who receive myeloablative therapy.
Transplantation of allogeneic hematopoietic stem cells, an effective treatment for ...hematologic cancers,
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is limited by the availability of HLA-matched donors. The risk of severe graft-versus-host disease (GVHD) after the transplantation of bone marrow from unrelated donors or partially HLA-mismatched related donors is another drawback of the procedure.
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Umbilical-cord blood is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children.
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Grafts of umbilical-cord blood reconstitute hematopoiesis more slowly than does HLA-matched marrow from a sibling or an unrelated adult donor,
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but the incidence and severity of GVHD are lower with transplantation . . .
Currently, granulocyte colony stimulating factor (G-CSF) remains the standard mobilizing agent for peripheral blood stem cell (PBSC) donors, allowing the safe collection of adequate PBSCs from the ...vast majority of donors. However, G-CSF mobilization can be associated with some significant side effects and requires a multi-day dosing regimen. The other cytokine approved for stem cell mobilization, granulocyte-macrophage colony stimulating factor (GM-CSF), alters graft composition and may reduce the development of graft-versus-host disease, but a significant minority of donors fails to provide sufficient CD34+ cells with GM-CSF and some experience unacceptable toxicity. AMD3100 is a promising new mobilizing agent, which may have several advantages over G-CSF for donor mobilization. As it is a direct antagonist of the interaction between the chemokine stromal-derived factor-1 and its receptor CXCR4, AMD3100 mobilizes PBSCs within hours rather than days. It is also well tolerated, with no significant side effects reported in any of the clinical trials to date. Studies of autologous and allogeneic transplantation of AMD3100 mobilized grafts have demonstrated prompt and stable engraftment. Here, we review the current state of stem cell mobilization in normal donors and discuss novel strategies for donor stem cell mobilization.
Despite more than 40 years of extensive study, it remains uncertain which individuals, if any, with acute myelogenous leukemia (AML) in first remission should receive a blood cell or bone marrow ...transplant versus post-remission chemotherapy (or both). Nevertheless, there is a recent trend toward recommending more transplants in this setting. We consider four myths underlying this recommendation: (1) only individuals achieving second remission benefit from a transplant; (2) there is no effective therapy for relapse other than an allotransplant; (3) we can accurately predict which individuals with AML in first remission need a transplant; and (4) detection of minimal residual disease in first remission will resolve this controversy. We discuss these misconceptions and suggest approaches to resolve this issue.
This large, randomized, multicenter trial compared voriconazole, a second-generation triazole, with liposomal amphotericin B as empirical antifungal therapy for 837 patients with persistent fever and ...neutropenia. The success rates in terms of composite outcome were similar: 26.0 percent with voriconazole and 30.6 percent with amphotericin B. There were fewer breakthrough fungal infections among those treated with voriconazole (1.9 percent vs. 5.0 percent).
In this large, randomized trial, the success rates were similar with voriconazole and with amphotericin B.
Invasive fungal infections are important causes of morbidity and mortality among patients receiving cancer chemotherapy or undergoing bone marrow or stem-cell transplantation.
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Over the past two decades, empirical antifungal therapy with conventional amphotericin B or liposomal amphotericin B has become the standard of care in reducing invasive fungal infections in patients with neutropenia and persistent fever.
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Amphotericin B, however, is associated with significant dose-limiting nephrotoxicity and infusion-related reactions. Liposomal amphotericin B is equivalent to conventional amphotericin B for use as empirical antifungal therapy and significantly reduces proven invasive fungal infections, nephrotoxicity, and infusion-related reactions.
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The high acquisition . . .
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