الفهرس 
History of Hematopoietic Stem Cell TransplantationOnly 14 pages are availabe for public view
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Abstract
Hematological malignancies currently represent the main indications for hematopoietic stem cell transplantation (HSCT). Clearly, autologous and allogeneic HSCT are established therapy in many situations and are integrated in the therapeutic strategy of most large multicenter cooperative study group trials.
In ALL; The critical factor in improving survival in adults with ALL is identifying patients with high-risk phenotypes in order to allow planning for early-allogeneic HSCT. Initiating a donor search while initial remission induction is underway can facilitate transplantation during CR1, when long-term results are best. For patients presenting with high-risk disease t(9;22), t(4;11), mature B cell, high WBC or for those failing to promptly achieve remission, allografts in CR1 offer the most important opportunity to achieve extended LFS. Finding the right sibling match or alternatively, a well-matched URD or closely matched single or pair of UCB units can permit the curative potential of allogeneic transplantation. Monitoring of minimal residual disease, utilization of targeted therapy, tyrosine kinase inhibitors, or newer agents yet to come, might further reduce missed opportunities for disease control and improved survival. Reduced intensity conditioning for the older or sicker patient, augmented conditioning, or novel radiation delivery for those with higher risk disease also offer promise yet need to be tested in prospective, well-designed clinical trials. Based on the current data, and understanding of the benefits and limits of each approach.
In AML; Success of chemotherapeutic regimens is largely dictated by cytogenetic risk and age. Chemotherapy is potentially curative for APL and core-binding factor (CBF) leukemia (good-risk cytogenetics). Patients with poor-risk cytogenetics should be offered transplant in CR1, and patients with intermediate risk should entertain the idea. Of note is that “elderly” AML patients have terrible outcomes with chemotherapy alone, and thus are candidates for an RIC transplant if there disease can be placed into a remission. Results for transplantation in CR1 are predictably better than cases that relapse, are in CR2, or have refractory AML.
Although a matched sibling donor is preferred as the stem cell source, equal results can be obtained with a fully matched–unrelated donor. Moreover, it appears that UCB transplants afford similar results as MRD or MUD transplants. Allogeneic SCT using related haploidentical donors is still investigational, with success mostly limited to patients who have myeloid malignancies in remission at the time of SCT.
Autologous transplantation for AML has been explored as consolidation for patients in CR1 or CR2. Patients undergoing autologous transplantation in CR1 have a decreased rate of recurrence compared with those receiving conventional chemotherapy but a higher recurrence rate than patients undergoing allogeneic transplantation. Patients with residual disease are at a higher risk of relapse compared with those without residual disease; thus, it is tempting to use MRD as a guide to suggest which patients should undergo transplant in remission.
As regards chronic lymphocytic leukemia; HSCT has a role to play in selected patients, with major focus on the use of RIC allogeneic HSCT. Although RIC HSCT appears to result in high response rates and eradication of PCR detectable MRD, the follow-up of most clinical trials is too short to assess whether HSCT can cure CLL.
Future approaches to the management of this disease must take into account the balance between the increased morbidity and mortality of HSCT in CLL with the curative potential that these approaches potentially offer, in the setting of the improvements in outcome that can now be seen using chemoimmunotherapy.
In the absence of any other treatment modalities currently capable of improving outcome in this disease, HSCT should be considered as a treatment approach for younger patients with high-risk CLL early in the course of the disease.
High-risk patients include those requiring treatment who have p53 abnormalities, patients who fail to achieve CR or who progress within 12 months after purine analogs, those who relapse within 24 months after having achieved a response with purine-analog-based combination therapy, those who have relapsed after prior autologous SCT, or those patients who are fludarabine refractory.
In CML; The last decade has witnessed a dramatic change in practice with a decline in the primary use of allo-SCT for CML after the introduction of TKI. Transplantation for chronic phase patients can be considered in the rare cases of intolerance to all TKI, and for those who acquire a T315I mutation. Because only a percentage of patients who become resistant become controlled with a second line agent, however, it is wise to begin the search for a donor when “salvage” therapy is started
Although TKI therapy, by itself or in combination with chemotherapy, can yield responses in advanced-phase CML, these regimens are not curative, and thus, patients who present or progress to accelerated or blast phase should be considered for transplantation
The decision for transplantation involves careful balancing of the risks for allo-SCT against the risk for disease progression in each individual patient. Transplantation for CML has not only benefited individual patients who have been cured as a consequence but has been hugely instructive in the fields of transplantation and immunotherapy. CML has been rightly described as a paradigm for malignancy and remains so as we work toward solving the remaining questions, not least of which are questions on the mechanisms of disease progression and the nature of the leukemic stem cell.