Allogeneic Hematopoietic Stem Cell Transplantation for Primary Myelofibrosis: A 20-year Experience in a Single Center

Background: Allogeneic hematopoietic stem cell transplantation is a well-established approach for patients diagnosed with primary myelofibrosis and remains the only potentially curative treatment. Aims: To present the overall outcome of patients with myelofibrosis treated with allogeneic hematopoietic stem cell transplantation. Study Design: A retrospective cross-sectional study. Methods: This study is a retrospective analysis of 26 consecutive patients with primary myelofibrosis who underwent transplantation at our center between January 2002 and January 2022. Disease and transplant variables contributing to outcomes were analyzed. Results: The median age at the time of transplantation was 52.5 (range, 32-63) years and the median time from diagnosis to allogeneic hematopoietic stem cell transplantation was 25 (range, 3.1-156.8) months. Myeloablative conditioning and reduced-intensity conditioning regimens were used in 8 (30.8%) and 18 (69.2%) transplantations, respectively. Neutrophil and platelet engraftment was achieved in 23 patients at a median follow-up of 21.2 months (range, 12 days to 234.8 months). Primary graft failure occurred in 1 of 23 patients (4.3%). Neutrophil and platelet engraftment occurred at a median of 16 (range, 12-39) days and 20 (range, 11-78) days, respectively. Acute graft-versus-host disease was seen in 11 of 22 patients engrafted allografts, of which 7 (31.8%) were grade 3-4 acute graft-versus-host disease. Eight patients (36.4%) developed chronic graft-versus-host disease, and three cases were extensive. Four patients (19%) relapsed after a median of 5.5 months, and three patients received donor lymphocyte infusion. The 3-year overall survival rate of the entire study population was 46.2%. The median overall survival was not reached in the myeloablative conditioning group; however, it was 11.9 months in the reduced-intensity conditioning group (p =0.3). According to the donor graft source, the median overall survival was 0.73 months in mismatched unrelated graft recipients, 12 months in matched sibling donors, and not reached in matched unrelated graft recipients (p = 0.03). The 3-year progression-free survival rate of patients who survived > 100 days was 74.7%. The effect of JAK-2 status, graft source, conditioning regimen or dynamic international prognostic scoring system on progression-free survival was not statistically significant. Conclusion: Given the poor prognosis of non-transplant recipients and the lack of non-transplant curative approaches, our results support the consideration of allogeneic hematopoietic stem cell transplantation for eligible patients with primary myelofibrosis.

Eltrombopag for the Treatment of Poor Graft Function Following Haematopoietic Cell Transplantation: Real-Life Data

Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre's experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x109/l (1-23), which increased to 41x109/l (6-150). The median platelet count increment was 29.5x109/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x109/l (0.39-5.1), which increased to 2.35 x109/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Alpha-1-Antitrypsin Experience for Steroid-Resistant Acute Graft-Versus-Host Disease.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) treatment has a low response rate and a high risk of infection in allogeneic hematopoietic stem cell transplantation. The standard approach to be applied in this situation is uncertain. This study aims to evaluate the effectiveness and safety of alpha-1-antitrypsin (AAT). In the study, the results of five SR-aGVHD patients received AAT evaluated. Complete response was seen 2 of four patients with gastrointestinal (GI) aGVHD, partial response in one GI and one liver aGVHD. The overall response rate was 80%. AAT is an effective and safe treatment option in SR-aGVHD.

Pretransplant Consolidation Therapies Improve the Outcome of Myeloablative Allogeneic Transplantation in Adults with Ph-negative Acute Lymphoblastic Leukemia.

BACKROUND AND AIM: The benefit of pre-transplant consolidation in patients with acute lymphoblastic leukemia (ALL) who achieved first complete remission (CR1) has not yet been clearly demonstrated. Here, we aimed to investigate the relationship between the treatments received before transplantation and transplant outcome in Ph-ALL patients who underwent myeloablative allo-HSCT in CR1. PATIENTS AND METHODS: A total of 55, 32 (58.2%) men and 23 (41.8%) women, who underwent allo-HSCT with the diagnosis of Ph-ALL were evaluated retrospectively. All patients underwent to allo-HSCT with myeloablative conditioning regimen in the 1st CR from the available donor. RESULTS: In patients who received >2 consolidation, the 2-year and 3-year OS was 69% and 65%, respectively, while the 2-year and 3-year OS was 39% and 26%, respectively, in those who received < 2 consolidation (P =.03). RFS was similar in both groups (P = .8). One year- NRM was found 28% in patients who received ≥ 2 consolidations, and 37% in patients who received <2 consolidation (P =.06). L-asparaginase, high dose methotrexate, and cranial treatments given before transplantation had no effect on transplant outcomes (P > .05). CONCLUSION: Contrary to the belief that pre-transplant consolidation is not beneficial in ALL patients who proceed with allo-HCST in CR1, our results showed that consolidation treatments reduce NRM and improve the survival.

Prospective Follow-up of Panel Reactive Antibodies From Diagnosis Until Completion of Therapy Including Allogeneic Stem Cell Transplantation Among Patients With Acute Leukemia.

OBJECTIVES: Existence of panel reactive antibodies is the limiting step in both solid-organ and hematopoietic stem cell transplantation. There are hypotheses related to panel reactive antibody formation, but there is no knowledge about its formation in acute leukemia at diagnosis and during the chemotherapy period, in which there is a strong myelosuppression and immunosuppression. We aimed to determine the panel reactive antibodies positivity in acute leukemia patients at diagnosis and during the entire therapy period, including stem cell transplantation. MATERIALS AND METHODS: In this single-center prospective study, we enrolled 35 patients with acute leukemia (8 with acute lymphoblastic leukemia, 27 with acute myeloid leukemia). Serum samples were obtained before induction therapy and every 3 months thereafter until the last follow-up or death, for a median of 369 days (minimum-maximum, 9-725 days). Panel reactive antibodies were defined with single-antigen bead assays on a Luminex platform. RESULTS: A total of 10 patients (29%) were found to have panel reactive antibodies at any time point. At diagnosis, 5 patients (14.3%) had antibodies of either class I (n = 2) or II (n = 1) or both (n = 2), and in 4 patients these persisted during median follow-up of 168 days (minimum-maximum, 9-322 days). Among the remaining 30 patients, an additional 5 (17%) developed de novo antibodies. Incidence rate of development of de novo antibodies was 5.5 per 10 000 person-days. There was no effect of transfusion load on the development of panel reactive antibodies. Differences in percentages in males versus females, blood type mismatch, and graftversus-host disease were higher in patients who had de novo antibodies after transplantation. Positivity at any time had no statistically significant effect on overall survival (P = .71). CONCLUSIONS: Panel reactive antibodies do not occur frequently in the acute leukemia setting despite intensive transfusions.

Treatment Approaches for Managing Patients with Hematological Malignancies in the Time of COVID-19 Pandemic.

Background/aim: The COVID-19 pandemic is a unique challenge to the care of patients with hematological malignancies. We aim to provide supportive guidance to clinicians making individual patients decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. Conclusion: This review also provides recommendations, which are convenient in evaluating indications for therapy, reducing therapy-associated immunosuppression, and reducing healthcare utilization in patients with specific hematological malignancies in the COVID-19 era. Specific decisions regarding treatment of hematological malignancies will need to be individualized, based on disease risk, risk of immunosuppression, rates of community transmission of SARS-CoV-2, and available local healthcare resources.

Thyroid dysfunctions in adult patients after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Thyroid dysfunction (TD) is one of the major endocrinopathies shown after allogeneic hematopoietic stem cell transplantation over the long term. The incidence and the risk factors for TD have varied widely. PATIENTS AND METHODS: Two hundred and fifty-nine patients with pre-transplant normal thyroid function tests who survived at least 1 year after allo-HSCT between 2006-2016 were included in the study. RESULTS: Sixty-four patients (25%) developed TD at median of 34 months (range, 1-112 months). Hypothyroidism was detected in 32 patients (12%): 5 patients had primary hypothyroidism, and subclinical hypothyroidism occurred in 27 patients. 18 patients (7%) were diagnosed with hyperthyroidism: 2 patients (0.07%) were treated for primary hyperthyroidism, and 16 patients (6%) were followed for subclinical hyperthyroidism. Euthyroid sick syndrome occurred in 14 cases. None of the patients with thyroid dysfunction developed secondary thyroid malignancy. Receiving high-dose TBI (P = .001) was found to be significant risk for hypothyroidism; older age than median (P = .01) and pre-transplant active disease (P < .0001) were related to hyperthyroidism. CONCLUSIONS: Thyroid dysfunction, mostly hypothyroidism, is a long-term complication after allo-HSCT in 25% of patients. Older age, pre-transplant active disease, and receiving TBI are among the risk factors. Sustained long-term monitoring of thyroid function test should be considered post allo-HSCT.

Graft-versus-cancereffect and innovative approaches in thetreatment of refractory solid tumors

Background/aim: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been used for the treatment of various refractory solid tumors during the last two decades. After the demonstration of graft-versus-leukemia (GvL) effect in a leukemic murine model following allo-HSCT from other strains of mice, graft-versus-tumor (GvT) effect in a solid tumor after allo-HSCT has also been reported in a murine model in 1984. Several trials have reported the presence of a GvT effect in patients with various refractory solid tumors, including renal, ovarian and colon cancers, as well as soft tissue sarcomas [1]. The growing data on haploidentical transplants also indicate GvT effect in some pediatric refractory solid tumors. Novel immunotherapy-based treatment modalities aim at inducing an allo-reactivity against the metastatic solid tumor via a GvT effect. Recipient derived immune effector cells (RDICs) in the antitumor reactivity following allo-HSCT have also been considered as an emerging therapy for advanced refractory solid tumors. Conclusion: This review summarizes the background, rationale, and clinical results of immune-based strategies using GvT effect for the treatment of various metastatic and refractory solid tumors, as well as innovative approaches such as haploidentical HSCT, CAR-T cell therapies and tumor infiltrating lymphocytes (TIL).

Current approach to early gastrointestinal and liver complications of hematopoietic stem cell transplantation.

The gastrointestinal (GI) system is one of the most commonly affected sites during a hematopoietic stem cell transplantation (HSCT) due to toxicities of preparative regimens, the accompanying immunodeficiency, and organ damage caused by graft versus host disease. In this review, we focus on early GI and liver complications following autologous (auto-) and allogeneic (allo-) HSCT and clarify both the risk factors and therapeutic strategies. Early GI and liver complications associated with HSCT remain challenging issues. Despite the improvements in this field during the last decade, treatments for these complications still place a significant burden on both patients and the physicians treating these patients. GI and liver complications remain some of the causes of mortality associated with HSCT. For practicing hematologists, oncologists, and gastroenterologists in this field, the awareness and early diagnosis of the GI complications remain important factors to obtain optimal outcomes in this patient population.

Contemporary patient-tailored treatment strategies against high risk and relapsed or refractory multiple myeloma.

Recurrence of disease due to chemotherapy drug resistance remains a major obstacle to a more successful survival outcome of multiple myeloma (MM). Overcoming drug resistance and salvaging patients with relapsed and/or refractory (R/R) MM is an urgent and unmet medical need. Several new personalized treatment strategies have been developed against molecular targets to overcome this drug resistance. There are several targeted therapeutics with anti-MM activity in clinical pipeline, including inhibitors of anti-apoptotic proteins, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, fusion proteins, and various cell therapy platforms. For example, B-cell maturation antigen (BCMA)-specific CAR-T cell platforms showed promising activity in heavily pretreated R/R MM patients. Therefore, there is renewed hope for high-risk as well as R/R MM patients in the era of personalized medicine.

Is there a role of high dose chemotherapy and autologous stem cell transplantation in the treatment of Ewing's sarcoma and osteosarcomas?

Although osteosarcomas are rare tumors, they are the most common primary bone tumors in children and adolescents younger than 20 years with a remarkable male predominance. Ewing's sarcoma (ES) is the second most common primary bone tumor in children and adolescents. The preferred actual treatment modality for osteosarcoma patients is neoadjuvant chemotherapy followed by complete surgical excision and adjuvant chemotherapy including agents such as doxorubicin, cisplatin, ifosfamide, and high-dose methotrexate which are widely used and accepted as being efficacious treatment strategies in osteosarcoma patients. Conventional treatments have increased overall survival (OS) rates in osteosarcoma and ES, but not as enough as desired. High dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) may be beneficial in some subgroup of ES, including children with partial response to conventional chemotherapy and with poor-risk as well as metastatic ES. HDC and ASCT remain as a clinical option in patients with ES, but it is considered as an experimental treatment approach for patients with osteosarcoma. In this review, we discussed the current approach and role of HDC and ASCT in the treatment of osteosarcoma and ES and focused on the current literature data evaluating the treatment outcomes of some sub-groups of high risk patients.

A Review of Allogeneic Hematopoietic Stem Cell Transplantation in Metastatic Breast Cancer.

Breast cancer (BC) has a high mortality rate and metastatic BC is almost incurable despite hormonal therapy and chemotherapy. The second and third lines of chemotherapies usually yield transient responses and the median survival is generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have been extensively investigated in this setting. The presence of immune mediated anti-tumor effects referred to as graft-versus-tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have been clearly defined. The advantages of allogeneic HSCT over autologous HSCT for metastatic BC are i) cancer-free graft and ii) immune-mediated GvT effects mediated by human leukocyte antigen compatible donor T-cells. In conclusion, a GvT effect does exist against metastatic BC and play a key role in tumor response. This review aims to describe the background, rationale, and clinical results of allogeneic HSCT as a potential alternative treatment in metastatic BC.

Is cytomegalovirus a risk factor for haemorrhagic cystitis in allogeneic haematopoietic stem cell transplantation recipients?

BACKGROUND: Haemorrhagic cystitis (HC) is usually a serious complication in allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients. In this study, our aim was to define risk factors and outcomes for patients with HC in an allo-HSCT setting. METHODS: We retrospectively evaluated 249 allo-HSCTs performed between 2011 and 2016 in our centre. RESULTS: HC was diagnosed in 98 patients (39%) at a median of 119 days (range 5-580) and 91 (93%) of the patients had late onset disease. In univariate analysis, HC was related to cytomegalovirus (CMV) reactivation (P<0.001) and BK viraemia (P<0.001); in multivariate analysis, the presence of CMV reactivation was determined to be an independent risk factor (odds ratio: 22.1; 95% CI 1.73, 282.44; P=0.017). There was no association detected between acute graft versus host disease and patients diagnosed with HC within 100 days of transplant. HC was significantly increased by the presence of myelo-ablative conditioning (odds ratio: 31.28; 95% CI 3.98, 246.87; P=0.001) and BK viraemia (odds ratio: 3.93; 95% Cl 1.10, 14.05; P=0.035) in patients with HC grade II and beyond. Forced hydration was recommended in all patients with grade I HC. Patients with HC and clots were treated with continuous bladder irrigation, and 14 of 44 patients with BK viraemia received cidofovir ± ribavirin. Eight of these patients (57%) responded to treatment. Refractory HC was detected in 17 patients (17%) and resolved by a variety of procedures. CONCLUSIONS: This study suggests that CMV reactivation is associated with increased risk of HC in multivariate analysis, however, this result is not confirmed in patients with HC grade II and beyond.

Adult Stem Cells and Medicine.

Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research. However, stem cell research field is developing so fast that, innovative approaches using HSCs for treatment of refractory diseases are growing rapidly. Hematopoietic stem cell transplantation (HSCT) has been widely used to achieve cure in different hematological diseases. Applications include the treatment of marrow failure syndromes, leukemia, lymphoma, multiple myeloma (MM), certain inherited blood disorders, autoimmune diseases and as an enzyme replacement in metabolic disorders. Innovative approaches such as haploidentical stem cell transplantation, new monoclonal antibodies and immunotherapies as well as Chimeric Antigen Receptor T-cell (CAR-T cell) therapies are on the way as promising treatment options especially for patients with refractory hematologic malignancies and even in solid tumors. However, there are still some challenges remaining before some of these therapies are translated into clinical application. In this paper, HSCs including its properties, niches, clinical usage and its contribution to modern medicine today and in the future will be discussed.

Current Approach to Non-Infectious Pulmonary Complications of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation is an established treatment for patients with a wide range of malignant and nonmalignant conditions. Noninfectious pulmonary complications still remain a leading cause of morbidity and mortality in these patients. Treating hematopoietic stem cell transplantation recipients with noninfectious pulmonary complications is still challenging, and the current treatment armamentarium and strategies are not adequate for patients receiving hematopoietic stem cell transplantation. Further trials are needed for a better description of the pathogenesis and the complete diagnostic criteria as well as for the development of effective therapeutic approaches for the management of noninfectious pulmonary complications of the hematopoietic stem cell transplantation. This review outlines the incidence, risk factors, pathogenesis, and clinical spectrum and discusses the current approaches to the management of noninfectious pulmonary complications of Hematopoietic stem cell transplantation.

Treatment with methotrexate, rituximab, and cytosine arabinoside followed by autologous stem cell transplantation in primary central nervous system lymphoma: A single-center experience.

OBJECTIVE/BACKGROUND: Primary central nervous system lymphoma (PCNSL) is associated with worst prognosis compared with other aggressive non-Hodgkin's lymphomas. However, recent trials have demonstrated that long-term progression-free survival can be achieved by immunochemotherapy. Our goal is to present our experience in aggressive PCNSL in this study. METHODS: We retrospectively evaluated the clinical features and management of 13 PCNSL patients who were diagnosed and treated between 2006 and 2015. RESULTS: Nine patients received rituximab (R) 375mg/m2/day on Day 1, methotrexate (MTX) 3.5g/m2/day and cytosine arabinoside (ARA-C) 4.4g/m2/day on Day 2, as well as ARA-C 4.4g/m2/day on Day 3 every 28days, and underwent autologous stem cell transplantation. Two patients received procarbazine instead of ARA-C. One patient relapsed, and allogeneic hematopoietic stem cell transplantation was performed. All nine patients are followed in complete remission. Two of 13 patients received one course of MTX and 36-45Gy radiotherapy and died. One patient with renal transplantation had progressive disease and died. Grade 3-4 hematological toxicity was detected in 11 (85%), Grade 3-4 mucositis in 11 (85%), and febrile neutropenia in 12 (92%) patients. The median overall survival in the R-MTX-ARA-C/procarbazine group was 28±16months. CONCLUSION: R-MTX-ARA-C followed by autologous stem cell transplantation seems a promising strategy with high response rates in PCNSL.

Current strategies for the management of autologous peripheral blood stem cell mobilization failures in patients with multiple myeloma.

Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation (AHSCT) worldwide. The collection of PBSCs is the essential step for AHSCT. The limits for minimum and optimum CD34+ cells collected have been accepted as 2 × 106 /kg and ≥4 × 106 /kg for single AHSCT; 4 × 106 /kg and ≥8-10 × 106 /kg for double AHSCT. Despite the success of conventional methods for PBSC mobilization in MM, mobilization failure is still a concern depending on patient age, duration of disease, and the type of induction therapy. By definition, "proven poor mobilizer" is the occurrence of mobilization failure (CD34+ cell peak <20/µL peripheral blood) after adequate preparation (after 6 days of G-CSF 10 µg/kg body weight alone or after 20 days of G-CSF >5 µg/kg body weight following chemotherapy) or a CD34+ cell yield of <2.0 × 106 /kg body weight after three consecutive apheresis. "Predicted poor mobilizer" involves (1) a failure of a previous collection attempt OR (2) a previous history of extensive radiotherapy or full courses of therapy affecting mobilization OR (3) the presence of at least two of the following features: advanced disease (>2 lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity of 30% at the time of mobilization or age >65 years. This article aims at discussing the risk factors for mobilization failure in the era of novel antimyeloma drugs, defining the poor mobilizer concept and summarizing the current and future strategies for the prevention and management of mobilization failures in MM.

A review of late complications of allogeneic hematopoietic stem cell transplantations.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment of different malignant and non-malignant diseases. Early transplant-related mortality after allo-HSCT has decreased with reduced-intensity conditioning regimens and effective anti-infectious treatments, but late transplant-related mortality is still a problem. Physicians are now paying more attention to late complications that may worsen the quality of life of many transplant recipients. Chronic graft versus host disease (cGVHD) is one of the major causes of late transplant-related mortality after allo-HSCT. This review discusses recent advances that have been made in clinical evaluation and treatment of late transplant-related complications including cGVHD. The different sites of involvement are organs, especially the skin and eye, and the gastrointestinal, endocrinologic, metabolic, renal, cardiologic, pulmonary, connective tissue, and neurological systems. In addition, this review includes infections and secondary malignancies in post-transplant settings that worsen quality of life in long-term follow-ups.

An overview of high dose chemotherapy with autologous stem cell rescue for germ cell tumors in current practice.

Testicular cancer is a frequent tumor of adolescent and young adult males. Chemotherapy has been reported to provide cure rates as high as 80% even in the presence of advanced testicular cancer. Studies regarding testicular cancer started after the advent of high dose chemotherapy (HDC) plus atologous stem cell rescue (ASCR) for the treatment of solid tumors in 1980s. Testicular cancer is highly responsive to HDC. Einhorn et al. have reported long-lasting remissions reaching up to 40% among patients with platinum-refractory disease. However, the present prospective randomized studies are heterogeneous in terms of patient characteristics and methodology, therefore superiority of HDC plus ASCR to conventional chemotherapies could not be proven. The results of the TIGER study, which is a recent prospective randomized study being conducted by the European Organisation for Research and Treatments in Cancer (EORTC) and the European Society for Blood and Marrow Transplantation (EBMT) aiming to compare HDC plus ASCR to conventional chemotherapy are eagerly expected. In this review, we will evaluate the current use of HDC plus ASCR in patients with relapsed or refractory germ cell tumors.