High-dose Chemotherapy Autologous Stem Cell Transplantation Research Articles

Primary intracranial germ cell tumors in adolescents and adults: Results of an international, multicenter, retrospective cohort study.

2061 Background: Primary Intracranial Germ Cell Tumors (iGCT) are rare. Previous prospective and retrospective studies mainly included pediatric patients (pts) with a median age of 10-14 years. The aim of this retrospective analysis was to evaluate characteristics, treatment and outcome of adolescents and adults with iGCT. Methods: Data were collected from 10 institutions in Germany and Switzerland. Pts aged >/= 16 years at first diagnosis or at relapse with a primary iGCT were included. Objective responses were evaluated by local investigators. Statistics (Cox proportional hazard model, progression-free survival (PFS) and overall survival (OS) analyzed by Kaplan-Meier method) were performed with SPSS v29. Results: We identified 75 pts (92.0% male) with a median age of 23 years (range 16-60, 94.7% >/= 18 years). At first diagnosis, histology was pure germinoma in 70.7%, pure teratoma in 10.7%, other non-germinomatous GCT (NGGCT) in 13.3%, unknown in 5.3% of pts. Localized, bifocal, and metastatic disease was found in 72.0, 6.7, and 21.3% of pts. As part of their first line (1L) treatment, 69.3%, 80.0%, and 62.7% received surgery, radiotherapy, and chemotherapy, respectively. High dose chemotherapy/ autologous stem cell transplantation (HDCT/ASCT) was part of 1L treatment in n=3 pts with NGGCT. Trimodal and bimodal treatment was performed in 48.0% and 32.0% of pts. Response to 1L therapy was complete remission (CR) in 61.3%, partial remission tumor marker negative (PRm-) in 16.0%, PRm+ in 4.0%, PR with tumor marker status unknown in 4.0%, progressive disease (PD) in 2.7%, and unknown in 12.0%. Relapse occurred in 13/75 pts (17.3%) with unknown histology (n=4), teratoma (n=2), other NGGCT (n=4), and germinoma (n=3). In 2 pts. in whom germinoma was diagnosed at time of first diagnosis, at time of recurrence PNET and Yolk sac tumor were histologically proven. Median time to relapse was 19.0 months (mo.; range 3-223). HDCT/ASCT as salvage treatment was performed in 5 pts with NGGCT and in one pt with germinoma as 2L (n=5) or 3L (n=1). NGGCT histology was associated with increased risk for recurrence or death (p=0.012 and 0.039).3-year PFS was 90.7% (germinoma: 98.1%, NGGCT: 73.9%) and 5-year OS was 92.0% (germinoma: 98.1%; NGGCT: 78.3%). Median follow-up time was 60 mo (range 0-339). Conclusions: Disease characteristics, treatment and outcomes of adolescent/ adult iGCT pts are comparable to those reported in pediatric pts. High cure rates are achieved in pts with pure germinoma and current treatment concepts. In pts with NGGCT further investigation is needed to improve survival outcomes.

Salvage Autologous Transplant and Lenalidomide Maintenance Versus Continuous Lenalidomide/Dexamethasone for Relapsed Multiple Myeloma: Long Term Follow up Results of the Randomized GMMG Phase III Multicenter Trial Relapse

Introduction The randomized, controlled, multicenter, phase III GMMG ReLApsE trial compared lenalidomide/dexamethasone (Rd) re-induction, salvage high dose chemotherapy, autologous stem cell transplantation (HDCT/ASCT) and lenalidomide (R) maintenance with standard continuous Rd. We have previously reported the absence of a significant survival benefit in the primary analysis. However, landmark analyses from salvage HDCT performed due to the fact that ~30% of patients in the HDCT arm did not receive salvage HDCT/ASCT suggested a survival benefit in patients undergoing salvage HDCT/ASCT. Here we report long term follow up results from the GMMG ReLApsE trial. Methods Between 2010 and 2016, 282 patients were randomized of whom 277 constituted the intention-to-treat (ITT) population (arm B/A n=139/138). Arm B received 3 cycles of Rd (lenalidomide 25 mg, day 1-21; dexamethasone 40 mg, day 1, 8, 15, 22; 4 week cycles) re-induction, HDCT (melphalan 200 mg/m 2), ASCT and R maintenance (10 mg daily) until progression (PD). Arm A was treated with Rd until PD. Key inclusion criteria were 1-3 prior treatment lines, age ≤ 75 years, time to PD ≥ 12 months in case of front-line HDCT/ASCT and WHO PS ≤ 2. R-refractory disease was not permitted and only 30/277 patients (11%) were previously exposed to R. The primary endpoint was progression free survival (PFS). Protocol-specified long term follow up collection included overall survival (OS), further lines of treatment and further salvage HDCT/ASCT after trial participation. ISRCTN16345835, Eudra CT-No: 2009-013856-61. Results Within the extended follow up period of 99 months, 238 PFS events (86%) and 174 deaths (63%) occurred. Median PFS in the ITT population was 20.5 months in arm B and 19.3 months in arm A without a statistically significant difference (HR 0.98; 95% CI 0.76-1.27; p=0.9). Median OS was 67.1 months in arm B vs. 62.7 months in arm A (HR 0.89; 95% CI 0.66-1.20; p=0.44). The absence of a significant PFS and OS benefit was consistent among key disease subgroups according to age, R-ISS, renal function, frontline single vs. tandem HDCT/ASCT, prior lines of treatment and prior maintenance treatment post HDCT/ASCT. Time to progression after frontline HDCT/ASCT was significantly associated with PFS in the total ITT population (p=0.001) as well as in both trial arms independently, but was not associated with a survival benefit from arm B vs. A (interaction test PFS p=1.0, OS p=0.7). Multivariate analyses revealed significant associations of survival with age (PFS: HR 0.8, p=0.045), high risk cytogenetic aberrations (PFS: HR 2.1, p<0.001; OS: HR 2.5, p<0.001), ISS stage III vs. I (OS: HR 2.0, p=0.02), elevated LDH (PFS: HR 1.5, p=0.04; OS: HR 2.1, p<0.001), >1 prior lines of treatment (PFS: HR 2.3, p=0.003), and no prior HDCT/ASCT (PFS: HR 1.8, p=0.04; OS: HR 2.2, p=0.009), but not with treatment arm B vs. A (PFS: HR 0.9, p=0.4; OS: HR 0.9, p=0.37). In landmark analyses from HDCT and the contemporaneous Rd cycle 5 in arm A (median interval from randomization to HDCT/Rd cycle 5: 117/122 days; n=103[B]/114[A]) no significant differences in PFS (23.0 vs. 20.3 months; HR 0.91; 95% CI 0.68-1.22; p=0.52) or OS (76.3 vs. 66.0 months; HR 0.8; 95% CI 0.56-1.13; p=0.2) in arm B vs. A were observed. Further lines of treatment after trial participation were reported in 88/139 (63%) and 96/138 (70%) patients in arm B and A (p=0.31). Significantly more salvage HDCT/ASCT were administered after trial participation in arm A vs. B (48/138 [35%] vs. 19/139 [14%], p<0.001). Immunomodulatory drug (lenalidomide, pomalidomide) based regimens were used comparably after both trial arms. The rate of second primary malignancies was comparable in arm B and A (26/139 [19%] vs. 19/138 [14%], p=0.3). Conclusions The GMMG ReLApsE trial is the only randomized, controlled trial comparing salvage HDCT/ASCT with continuous novel agent treatment. With extended follow up, no significant PFS or OS difference is observed in the overall trial population and the previously reported survival benefit in patients who actually received salvage HDCT/ASCT is not confirmed. Time to progression after frontline HDCT/ASCT which is frequently used to stratify for salvage HDCT/ASCT in clinical practice is a general prognostic parameter for PFS, but does not predict benefit from salvage HDCT/ASCT vs. continuous Rd treatment. The GMMG ReLApsE trial does not support salvage HDCT/ASCT for relapsed or refractory multiple myeloma.

Survival Outcomes for Patients with Relapsed/ Refractory Aggressive B Cell Lymphomas Following Receipt of High-Dose Chemotherapy/Autologous Stem Transplantation and/or Chimeric Antigen Receptor-Modified T Cells

Patients diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) may achieve prolonged survival following receipt of high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) or CD19-directed chimeric antigen receptor modified T cell therapy (CART19). Although early results from randomized clinical trials suggest that assignment to CART19 versus salvage immunochemotherapy as second-line therapy results in improved survival, analysis of a large series of patients who actually received HDC/ASCT or CART19 has yet to be performed. Such an analysis may inform future research efforts to optimize the risk stratification of R/R DLBCL/HGBL patients who are candidates for either therapy. The aim of this study was to evaluate clinicopathologic factors predictive of freedom from treatment failure (FFTF) for R/R DLBCL/HGBL patients following receipt of HDC/ASCT or CART19, and to compare patterns of treatment failure (TF) in R/R DLBCL/HGBL patients receiving HDC/ASCT and those receiving CART19. THE STUDY GROUP COMPRISED: patients age ≤75 years with R/R DLBCL/HGBL who received HDC/ASCT demonstrating partial or complete metabolic response to salvage immunochemotherapy and/or CART19 in the standard of care setting at the University of Pennsylvania between 2013 and 2021. Survival analyses were performed from the time of infusion of either HDC/ASCT or CART19, as well as at landmark time points postinfusion for patients who achieved FFTF. For 100 HDC/ASCT patients with a median follow-up of 62.7 months, the estimated 36-month FFTF and overall survival (OS) rates were 59% and 81%, respectively. For 109 CART19 patients with a median follow-up of 37.6 months, the estimated 36-month FFTF and OS rates were 24% and 48%, respectively. HDC/ASCT patients had significantly higher rates of estimated 36-month FFTF when they achieved actual FFTF at 3, 6, 12 and 24 months. Additionally, the rates of baseline characteristics predictive of TF at 36 months for either HDC/ASCT or CART19 patients were either similar to or significantly lower for CART19 patients compared to HDC/ASCT patients who achieved actual FFTF at 3, 6, 12, and 24 months. Patients with R/R DLBCL/HGBL achieving response to salvage immunochemotherapy who received HDC/ASCT had a high rate of estimated FFTF regardless of whether they harbored features predictive of resistance to salvage immunochemotherapy, which may be more durable than that of R/R DLBCL/HGBL patients receiving CART19. These findings support further investigation of disease characteristics, such as molecular features, that may predict response to salvage immunochemotherapy in patients fit for HDC/ASCT.

Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature.

Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities, including high-dose chemotherapy-autologous stem cell transplantation. The pivotal ZUMA-1 and JULIET trials that led to FDA approval of Axicabtagene ciloleucel and Tisagenlecleucel for relapsed refractory large cell lymphoma excluded patients with CNS involvement due to concerns of increased toxicity. However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients. In the real-world experience, chimeric antigen receptor T-cell (CAR T) therapy has been deemed safe and effective for these patients with poor prognosis. In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.

Outcomes of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Responded to Daratumumab, Pomalidomide and Dexamethasone (DPd), Followed By High Dose Chemotherapy/Autologous Stem Cell Transplantation (HDCT/ASCT) Versus (DPd) Alone

Background: Despite the many advances in the treatment landscape of relapsed refractory multiple myeloma (RRMM), survival outcomes remain poor for patients with triple class refractory disease (refractory to proteasome inhibitors (PIs), immunomodulatory agents (IMiDs) and anti-CD-38 monoclonal antibodies). While the role of autologous stem cell transplant (ASCT) in the first line therapy is well established, efficacy of ASCT for patients with RRMM in the era of novel therapeutic agents remains unknown. In this single center retrospective analysis, we compared the efficacy and safety outcomes of patients with RRMM treated with daratumumab, pomalidomide, and dexamethasone (DPd) alone versus (vs) DPd followed by ASCT. Methods: A total of 83 patients with RRMM who were treated and achieved at least partial response (PR) with DPd alone vs DPd followed by ASCT were evaluated by electronic medical records (EMR). DPd was given as daratumumab 16 mg/kg IV or 1800 mg SQ weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks; pomalidomide at 4 mg orally on days 1-21 of a 28-day cycle; and dexamethasone 20 or 40 mg weekly. Twenty-one patients who responded to DPd proceeded with melphalan 140 or 200 mg/m2 followed by ASCT and subsequent maintenance therapy. Responses were evaluated using the international myeloma working group (IMWG) response criteria. Patient and disease characteristics, as well as efficacy and safety outcomes were summarized using descriptive statistics. Kaplan-Meier analyses were used to estimate progression-free (PFS) and overall survival (OS). Results: A total of 21/83 (25%) pts with RRMM who achieved at least PR to DPd underwent ASCT (DPd/ASCT) while the remaining 62/83 (75%) continued DPd without ASCT (DPd alone). For the entire patient population, median age was 66 years [IQR 42-81]; 49 (59%) patients were male, 54 (65%) patients had IgG isotype, 21 (25%) patients had R- ISS stage III disease, 51 (61%) patients had high-risk cytogenetics, and 17 (20%) patients had extramedullary disease (Table 1). Patient age, disease stage, and cytogenetic risk profile was balanced between two groups. However, more patients in the DPd/ASCT group when compared to the DPd alone group had not received a prior ASCT (29% vs 15%) or had double refractory disease (67% vs 40%). All patients in this study had achieved at least a PR, though very good partial response (VGPR) or better was observed in 37 (60%) and 18 (86%) patients in the DPd alone and the DPd/ASCT group, respectively. Median PFS was 17.5 months (95%CI 10.3-32.1) with DPd alone vs 42.2 months (95%CI 36.4-NA) in the DPd/ASCT group (p=0.006). Median OS was 38.1 months (95%CI 25.0-NA) for DPd alone group vs not reached in the DPD/ASCT group (p=0.009, Figure 1,2). The most common grade 3 or 4 treatment related adverse events (TRAE) were neutropenia [49 (79%) vs 21 (100%)], anemia [11 (18%) vs 7 (33%)], thrombocytopenia [4 (96%) vs 7 (17%)], neutropenic fever [4 (6%) vs 11 (52%)], hospitalization secondary to TRAE [20 (32%) vs 14 (67%)] with the DPd vs DPd/ASCT groups, respectively. There was no treatment-related mortality in either group. Conclusion: Our retrospective analysis demonstrates patients who responded to DPd and underwent ASCT afterwards have superior PFS and OS compared to those who received DPd alone. Although DPd followed by ASCT is associated with more cytopenias and its related complications, this treatment appears to be overall safe for many patients with RRMM. These findings should not only be compared with larger multicenter collaborative registry-based data sets but also be tested in a prospective, randomized trial to ascertain the benefit of ASCT beyond the benefit observed by DPd alone. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Advances in current treatment for patients with newly diagnosed multiple myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of monoclonal plasma cells at multiple sites in the bone marrow, with accompanying alterations in the bone marrow microenvironment, and suppression of the host antitumor immune response, resulting in the uncontrolled accumulation of malignant plasma cells and excess secretion of immunoglobulins (paraproteins). MM, in almost all cases, is preceded by a premalignant phase, monoclonal gammopathy of undetermined significance (MGUS).1 MGUS is present in ∼3% of the population aged >50 years and progresses through asymptomatic smoldering myeloma to symptomatic MM at a rate of 1% annually.2 MM is usually diagnosed when the disease becomes symptomatic, classically presenting with bone pain, anemia, renal insufficiency, hypercalcemia and recurrent infections due to immune deficiency. MM has an annual age-adjusted incidence of 5.8 cases per 100 000 of the population and predominantly affects older individuals; the median age at diagnosis is 69 years.3, 4 MM is an incurable disease and the survival prognosis for patients diagnosed with MM has historically been poor. The introduction of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) in the 1980s improved response rates and progression-free survival (PFS), but median overall survival (OS) remained at 65 years for whom OS is only 26 months.8 The treatment of MM in elderly patients remains a clinical challenge—they are usually ineligible for stem cell transplantation and are unable to tolerate the toxicity of intense chemotherapy. Besides age at diagnosis and disease stage, prognosis is also adversely affected by the presence of several ‘high-risk' genetic markers, including deletions of chromosome 13, hypodiploidy and deletions of chromosome 17p, t(4;14) or t(14;16).2 Significant improvements in response rates, PFS and OS have been seen in patients with NDMM treated with combination regimens based on immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib).9, 10, 11, 12, 13, 14, 15, 16 These advances, coupled with an improved understanding of the disease, have shifted the treatment paradigm in MM. The current aim of this therapy for patients with NDMM is to achieve deep and long-term clinical remissions with early and continued use of regimens that are effective and safe to maintain disease control and extend OS. The purpose of this supplement is to review current approaches to the treatment of NDMM, providing an update on the most recent developments and treatment regimens involving the novel therapies, and highlighting the key issues that clinicians face when devising a long-term management strategy for NDMM patients. In the first article, Drs Munshi and Girnius provide an overview of the current approaches related to the diagnosis and management of MGUS, smoldering MM and MM, highlighting the need for a long-term approach to optimize disease control and the importance of a risk-stratified approach to treatment. In the second article, Drs Giralt and Bensinger discuss the role of ASCT and the role of novel therapies in induction treatment. The question of how to optimize the response to ASCT using consolidation therapy with novel agents is then addressed by Drs Moreau and Touzeau, including a review of recent clinical evidence showing the benefit of post-transplantation maintenance treatment with novel agents to extend PFS. Finally, Professor San Miguel and Dr Mateos provide an overview of the treatment options available for NDMM patients ineligible for HDT–ASCT because of either advanced age or comorbid conditions. Again, the focus is on the way in which the novel therapies have transformed the treatment options available to this population, who represent the majority of NDMM patients. In this setting, early and continued treatment with novel agents appears to have the potential to extend survival times for elderly and frail patients for whom outcomes have remained poor. Collectively, these articles illustrate how the introduction of novel agents, such as lenalidomide and bortezomib, has transformed the approach to treatment of NDMM and has provided a valuable clinical update for those working in this field.

Randomized Phase II Study of Bortezomib, Thalidomide, and Dexamethasone With or Without Cyclophosphamide As Induction Therapy in Previously Untreated Multiple Myeloma

Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety. Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy-autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.3 mg/m(2), thalidomide 100 mg, and dexamethasone 40 mg, with (n = 49) or without (n = 49) cyclophosphamide 400 mg/m(2) for four 21-day cycles, followed by HDCT-ASCT. The primary end point was postinduction combined rate of near-complete response (nCR) or better (including complete response [CR] with normalized serum κ:λ free light chain ratio, CR, and nCR). Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow-confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post-HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC). In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms). Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference post-transplantation versus baseline. Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.

PO38 Re-treatment versus rituximab maintenance therapy at progression in patients with follicular lymphoma

January 2010. The most common initial treatments was R-CHOP. Patients were required to have a CR following initial treatment to continue with Rituximab maintenance therapy which was administered as 375mg/m2 doses every 3 months for 2 years. Eighteen patients with aggressive subtypenon Germinal centre DLBCL were treated with high-dose chemotherapy/autologous stem cell transplantation (HDT/ASCT) and received rituximab maintenance therapy every 2 months for 2 years. Results: Most patients had disease stage according to Ann Arbor III. Event-free and overall survivals were 97.6 months and 100.8 months. To date, 67/80 patients are in continuous clinical remission and only 8 patients have relapsed, and 5 patients have died. Maintenance therapy was generally good tolerated: in 5 pts a WHO grade 3 toxicity event occurred which were arrhythmia, leucopenia, and infection. In one pt two WHO grade 3 toxicity events were observed (infection, neuropathy). Conclusions: Rituximab maintenance therapy is effective and well tolerated in this setting. Evaluation of a larger patient population, together with a longer follow-up, will determine whether this treatment approach has curative potential in aggressive lymphoma.

Rituximab Maintenance Therapy in CD20+ B-Cell Non-Hodgkin's Lymphoma.

Purpose: Clinical and pharmacokinetic data suggest that high serum concentrations of rituximab and prolonged exposure to rituximab are associated with higher response rates and improved quality of response. We used rituximab-maintenance therapy to target minimal residual disease, with the aim of increasing the duration of remissions achieved following initial treatment.Methods: During 2001–2005, 14 patients with CD20+ B-cell non-Hodgkin's lymphoma (seven with diffuse large B cell lymphoma [DLBCL] and seven with follicular lymphoma [FL]) were enrolled in the study. Patients with DLBCL and FL were required to have a CR or PR, respectively, following initial treatment. The most common initial treatments were R-CHOP, R-FC or CHOP. Rituximab-maintenance therapy was administered as 375mg/m2 doses every 3 months for 2 years. Three patients with aggressive DLBCL were treated with high-dose chemotherapy/autologous stem-cell transplantation (HDT/ASCT) and received rituximab-maintenance therapy every 2 months for four doses in total.Results: Most patients had disease of Ann Arbor stage ≥ 3 (two FL patients stage I). In patients with DLBCL, median event-free and overall survivals were 22.1 months and 22.3 months, respectively, with the corresponding values being 20.6 months and 26.1 months in patients with FL. To date, 13 patients are in continuous clinical remission and only one patient has relapsed.Conclusions: Rituximab-maintenance therapy is effective and well tolerated in this setting. Recruitment for this study is ongoing and evaluation of a larger patient population, together with a longer follow-up, will determine whether this treatment approach has curative potential.

Minimal residual disease in solid tumor malignancies: a review.

The increase in the number of patients treated with high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) for solid tumor malignancies has generated concern about the infusion of tumor cell contamination in the graft. In an effort to study so-called minimal residual disease (MRD) in the HDC/ASCT setting, a variety of assay methods have been used. Although these assays vary in terms of sensitivity and specificity of tumor detection, they are in agreement as to the presence and viability of tumor cells in ASCT grafts. A growing body of evidence indicates that MRD is present in ASCT grafts from neuroblastoma, breast cancer, and ovarian cancer patients. More importantly, several retrospective studies have determined that the infusion of tumor cells with the ASCT graft is strongly associated with post-ASCT relapse. Gene-marking studies have directly demonstrated that infused tumor cells are present at sites of disease relapse. Thus, the issue of tumor contamination of autologous grafts is an area of growing concern. This review article details the current status of MRD in solid tumor malignancies, with emphasis on assay methodology, clinical utility, and clinical relevance in transplantation medicine.