T-Cell Lymphoproliferative Disorders Following Allogeneic Bone Marrow Transplant: A Report of Two Cases and a Literature Review.

Post-transplantation lymphoproliferative disorders (PTLD) are a commonly occurring condition following solid organ transplantation (SOT) and, rarely, hematopoietic stem cell transplantation (HSCT). As the name suggests, a PTLD is a condition where there is a clonal proliferation of lymphoid cells that occurs as a complication after transplantation. Though the clonal origin cell is primarily associated with the B-cell lineage, there are existing cases in the literature describing PTLD from the T-cell lineage. Large granulocytic leukemia (LGL) is one rare T-cell lineage subtype that typically progresses with a passive clinical course and is discovered with leukocytosis and peripheral blood smears demonstrating large granules in lymphocytes. In this study, we describe two patients initially diagnosed with acute myeloid leukemia (AML) who were both found to have T-cell PTLD after undergoing allogeneic hematopoietic stem cell transplant. One was found with a clonal expansion of T-cells on flow cytometry and the other with LGL on peripheral blood and flow cytometry. This discovery was made at 16 and 20 months after their transplant respectively. Distinguishing factors for these two patients are demonstrated by the derivation of lymphoproliferative disorder from graft vs. host disease (GVHD) or viral etiology, which is significant as both of which have been shown to be associated with PTLD. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) positivity have been shown to be associated with PTLD, and both our patients were EBV-negative but had harbored prior CMV infections. Additionally, they had a benign course with no development of cytopenias or symptoms since the time of diagnosis. These two cases add to the growing literature that is working to better characterize the rare development of LGL and, in general, T-cell PTLD following allogeneic bone marrow transplantation.

A Case of Recurrent Multiple Myeloma as Testicular Plasmacytoma Without Systemic Disease.

Plasma cell neoplasms include various conditions ranging from indolent conditions such as monoclonal gammopathy of undetermined significance (MGUS) to more aggressive forms such as multiple myeloma (MM). The World Health Organization classifies plasmacytomas into two types: solitary osseous plasmacytoma (SOP) and extramedullary plasmacytoma (EMP). Most primary EMPs occur in the upper gastrointestinal tract, head and neck, upper respiratory system, central nervous system, lungs, liver, spleen, and kidneys. However, the occurrence of EMP involving the testis site is quite rare. Given the rarity of testicular plasmacytoma, there is no consensus on the standard of treatment for this diagnosis. Most EMP is radiosensitive, with few localized types responding to surgical intervention. Tumor recurrence and disseminated infiltration are treated with adjuvant chemotherapy after radiation or surgery. Our patient has a unique presentation of an individual who developed recurrent myeloma of the testis 12 years after his initial diagnosis of myeloma.

Pembrolizumab for patients with non-Hodgkin lymphoma: phase 1b KEYNOTE-013 study.

The multicohort phase 1b KEYNOTE-013 study (NCT01953692) evaluated the safety and efficacy of pembrolizumab in patients with relapsed or refractory NHL who were ineligible for or failed hematopoietic cell transplantation (HCT). Patients received pembrolizumab (cohort 4) or pembrolizumab plus lenalidomide (cohort 5). Primary end points were safety and objective response rate (ORR) per IWG 2007 criteria. Cohort 4 included 89 patients. ORR was 22% (19/86; 90% CI 15-31; 10 CR, nine PR); ORRs by disease type were 48% (10/21), 10% (2/20), 12% (5/41), and 50% (2/4), for PMBCL, FL, DLBCL, and 'other' NHL, respectively. Toxicity was as predicted. Cohort 5 included 19 patients. ORR was 39% (90% CI 20-61; four CR, three PR). Hematologic toxicities were the most common treatment-related AEs. In conclusion, pembrolizumab following HCT ineligibility/failure confirms prior experience in PMBCL but not with NHL subtypes in this study. Additional analyses in DLBCL may not be warranted.

A Review of the Abscopal Effect in the Era of Immunotherapy.

The abscopal effect is a systemic immune response mediated by the effects of radiation on the immune system. This effect has been observed in a number of cancer types in addition to lung cancer, including but not limited to renal cell carcinoma, hepatocellular carcinoma, lymphoma, and melanoma. The combination of radiation therapy and immune checkpoint inhibition (ICI) acts at several stages of the antitumor response, suggesting a mechanism of synergy between the two modalities. This review focuses on recent advances in the understanding of the effect of radiation and immunotherapy in the context of the abscopal effect.

Immunoglobulin Light Chain (AL) Amyloidosis Preceding Marginal Zone Lymphoma: A Case Report.

Immunoglobulin light chain (AL) amyloidosis is a systemic disease in which different systems such as kidneys, heart, and lungs are affected by the deposition of amyloid, a form of fibrillary protein. Usually, it occurs in patients with pre-existing diagnoses of plasma cell dyscrasias and is rarely seen in the concurrence of marginal zone lymphoma (MZL). Earlier interventions with cyclophosphamide and dexamethasone in conjunction with newer therapies such as bortezomib, carfilzomib or lenalidomide, and pomalidomide are being used to treat patients with AL amyloidosis. In this report, we are presenting a unique case of a patient who was diagnosed with AL amyloidosis several years prior to presenting with a soft tissue mass, which was subsequently noted to be an amyloid mass within an MZL. Overall, the occurrence of AL amyloidosis and MZL is rare with less than 20 patients reported. The MZL developed prior to or simultaneously with AL amyloidosis in the reported cases. Therefore, to our knowledge, this is the first time systemic amyloidosis has preceded MZL.

Pulmonary AL amyloidosis: A review and update on treatment options.

Amyloidosis is a rare disease that involves the extracellular deposition of abnormally folded proteins, precipitating organ dysfunction. Pulmonary amyloidosis is frequently characterized by the AL amyloid subtype and can be localized or associated with systemic involvement, presenting in a nodular, diffuse alveolar-septal, or tracheobronchial pattern. Presentation of disease can vary from clinically silent to severe. Pulmonary amyloidosis is typically first suspected on CT scan of the chest. Diagnostic workup requires tissue biopsy and identification by immunohistochemical staining. Systemic treatment has evolved over recent years to include the combination of daratumumab, bortezomib, cyclophosphamide, and dexamethasone (dara-VCD) as first-line therapy, with the goal of quickly attaining complete hematologic response. Through clinical vignettes, we review pulmonary AL amyloidosis and discuss current treatment options.

A phase 1/2 study of ixazomib in place of bortezomib or carfilzomib in a subsequent line of therapy for patients with multiple myeloma refractory to their last bortezomib or carfilzomib combination regimen.

Identifying effective combination regimens is a high priority in multiple myeloma (MM), as most patients eventually become refractory to their current treatments. In this study, we investigated whether the proteasome inhibitor (PI) ixazomib could delay disease progression among patients who failed regimens containing another PI, bortezomib or carfilzomib. This phase 1/2, multicenter, open-label, nonrandomized study enrolled patients who were refractory to a previous regimen containing bortezomib or carfilzomib. Patients continued the other anti-MM drugs in the regimen at the same doses and frequencies. Patients with combination regimens with unknown maximum tolerated dose (MTD) of ixazomib were enrolled in phase 1, with ixazomib starting at 3 mg and then dose escalated to 4 mg. Patients on regimens with a known ixazomib MTD were enrolled in phase 2. Primary endpoints were overall response rate (ORR), clinical benefit rate (CBR), adverse events (AEs), and determination of maximum tolerated dose (MTD). Of the 46 patients enrolled, 39 were evaluable for efficacy. ORR and CBR were 12.8% and 17.9%, respectively. Ixazomib appeared to be well tolerated as a replacement for carfilzomib and bortezomib, with 23.9% of patients experiencing at least one grade ≥3 serious adverse event (SAE) and 37.0% experiencing at least one grade ≥3 AE. The most common grade ≥3 AEs were hyponatremia (8.7%), anemia (8.7%), dyspnea (8.7%), thrombocytopenia (6.5%), dehydration (4.3%), and pneumonia (4.3%). The results indicate that ixazomib is not an effective replacement for bortezomib or carfilzomib for patients with MM who have previously relapsed on other bortezomib/carfilzomib-containing regimens.

Mantle Zone Lymphoma With Prostate Gland Enlargement: A Case Report.

The prostate is a rare site for the occurrence of lymphoma and accounts for 0.1% of newly diagnosed lymphomas. Patients with prostatic lymphoma exhibit similar symptoms to that of benign prostatic hyperplasia and prostate carcinoma, such as obstructive and irritative urinary signs. Therefore, due to its rare occurrence, it is difficult to distinguish between primary lymphoma of the prostate and other etiologies. We present a unique case of an elderly individual who presented with enlarged prostate and was found to, concurrently, have mantle zone lymphoma of the prostate.

Primary Central Nervous System Lymphoma With Systemic Recurrence.

Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin's lymphoma confined to the brain, leptomeninges, spinal cord, or eyes without systemic involvement. Nearly half of patients with PCNSL who achieve complete remission, relapse within five years. The majority of patients who relapse have a local recurrence. Systemic relapse, however, is much rarer. Here, we report a rare case of a 70-year-old male diagnosed with PCNSL who relapsed systemically nearly 1.5 years after achieving complete remission. His treatment consisted of chemoimmunotherapy and targeted therapy followed by an autologous transplant. Currently, there is no standard of care for systemic relapse of PCNSL. This multiagent treatment modality may be one such option for salvage therapy.

DA-REPOCH Versus R-CHOP for the Treatment of Activated B-Cell Subtype Diffuse Large B-Cell Lymphoma: A Community Center Experience.

Diffuse large B-cell lymphoma (DLBCL) represents around one quarter of non-Hodgkin lymphomas in both the United States and globally. The activated B-cell (ABC) subtype of DLBCL is associated with higher relapse rates and a worse prognosis when treated with standard regimens in comparison to other subtypes of DLBCL. Recent studies have demonstrated a potential benefit with combination of dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-REPOCH) in comparison to standard combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in ABC DLBCL patients. We aimed to see if there was any benefit on progression-free survival (PFS) and overall survival (OS) in a pooled patient population from a community oncology practice with the use of DA-REPOCH in ABC DLBCL. Our study did not reveal a statistically significant advantage in either PFS or OS with DA-REPOCH; however, a smaller percentage or patients progressed or relapsed when treated with DA-REPOCH. While the toxicity profile was similar, a higher percentage of patients receiving R-CHOP experienced grade 3 or higher toxicities. A prospective trial of R-CHOP versus DA-REPOCH in patients with the ABC subtype of DLBCL is warranted to further determine a potential benefit to DA-REPOCH in this patient population.

Therapy-Related Acute Myeloid Leukemia Following TCHP Chemotherapy in Two HER2+ Breast Cancer Patients.

Increased risk for the development of therapy-induced myeloid leukemia following the treatment of breast cancer has typically been associated with the use of regimens containing anthracyclines or alkylating agents. We present two cases of estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-positive (ER+/PR+/HER2+) breast cancer patients, treated with a non-anthracycline, non-alkylating regimen of trastuzumab, carboplatin, docetaxel, and pertuzumab (TCHP), who developed therapy-related acute myeloid leukemia (t-AML) within 30 months of the completion of treatment. Both patients had marked cytogenetic abnormalities, including deletions of chromosomes 5 and 7, and highly aggressive disease that resulted in a poor prognosis. While platinum and taxane-based chemotherapy regimens have been previously linked to the development of t-AML or therapy-related myelodysplastic syndrome (t-MDS) following treatment for ovarian cancer, they have not yet been shown to increase the risk of t-AML/t-MDS after their use for breast cancer therapy. As TCHP is widely used for the treatment of HER2/neu overexpressed breast cancer, these cases highlight the need to further evaluate the link between taxane and platinum-based chemotherapeutics for breast cancer and the development of t-AML/t-MDS.

Reducing Unwarranted Oncology Care Variation Across a Clinically Integrated Network: A Collaborative Physician Engagement Strategy.

PURPOSE: Addressing unwarranted clinical variation in oncology is a high priority for health systems that aspire to ensure consistent levels of high-quality and cost-effective care. Efforts to improve clinical practice and standardize care have proven challenging. Advocate Physician Partners undertook a patient simulation-based practice measurement and feedback project that was focused on breast and lung cancer to engage oncologists in the care standardization process. METHODS: One hundred three medical oncologists cared for online simulated patients using the Clinical Performance and Value platform, receiving feedback on how their care decisions compared with evidence-based guidelines and their peers. We repeated this process every 4 months over six rounds, measuring changes in quality-of-care scores. We then compared simulated patient results with available patient-level claims data. RESULTS: Over the course of the project, overall quality-of-care scores improved 11.9% (P < .001). Diagnostic accuracy increased 6.7% (P < .001) and correlated with improved treatment scores, including a nearly 10-percentage point increase in evidence-based chemotherapy regimens (P = .009) and a 56% increase in addressing palliative needs for patients with late-stage disease (P < .001). Unnecessary test ordering declined 25% (P < .001). We compared these results with available patient data and observed concordance with the metastatic imaging workup order rate for early-stage breast cancer. As unnecessary workups declined in the simulations and became more closely aligned with evidence-based guidelines, we saw similar rates of decline in the patient-level data. CONCLUSION: This study demonstrates that an oncology care standardization system that combines simulated patients with serial feedback increases evidence-based and cost-effective clinical decisions in patient simulations and patient-level data.

The Abscopal Effect Exists in Non-small Cell Lung Cancer: A Case Report and Review of the Literature.

The case of a 62-year-old woman who presented with stage IV adenocarcinoma of the left lung and a large left adrenal metastasis is presented. Following local radiation therapy to the left lung and nivolumab, she is now disease free 4.5 years from the time of the diagnosis. Five additional cases that have been reported are reviewed. The abscopal effect exists in non-small cell lung cancer (NSCLC) and has been reported with local radiation therapy alone as well as local radiation followed by either nivolumab or ipilimumab. Future randomized studies should address the synergist effects of local radiation therapy and the programmed cell death 1 (PD-1) checkpoint inhibitors versus the PD-1 checkpoint inhibitors alone.

A Retrospective Study of Double-hit Lymphomas in Elderly Patients (Aged > 70 Years): Overall Outcomes.

BACKGROUND: Double-hit lymphomas (DHLs) are high-grade diffuse large B-cell lymphomas with concurrent translocations involving myc and bcl-2 and/or bcl-6. A patient with DHL often has advanced disease at presentation and typically responds poorly to standard therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). More intensive treatment regimens have been studied; however, few data are available on the outcomes in elderly patients (aged > 70 years) treated with these therapies. We retrospectively studied the efficacy and tolerability of chemotherapy regimens in elderly patients within the Advocate Healthcare System. MATERIALS AND METHODS: A system-wide search of patients treated from 2012 to 2017 was completed to identify patients with c-myc with bcl-2 and/or bcl-6 translocations using fluorescence in situ hybridization. The patients were reviewed for the following: age at diagnosis, stage, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, chemotherapy details, grade 3/4 toxicities, and response to therapy. Overall survival (OS) and event-free survival (EFS) were calculated. RESULTS: We identified 17 patients (9 men and 8 women) with a median age of 73 years (range, 70-89 years). Six patients received R-EPOCH (rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin), 5 received R-CHOP, 1 received bendamustine and rituximab, 1 received the MaGrath regimen, and 1 received cyclophosphamide and rituximab. Three patients were not treated and were referred to hospice care. For all patients, the median follow-up period was 25 months, the EFS and OS were 28% at 36 months, and the median survival was 7.5 months. For patients treated with R-EPOCH, the EFS was 33% at 24 months. For the R-CHOP group, the EFS was 40% at 24 months. Most common grade 3/4 toxicities were neutropenia, anemia, thrombocytopenia, and infections and were more common in the R-EPOCH group. Three patients each died in the R-EPOCH and R-CHOP groups. CONCLUSION: Although the numbers are small, elderly patients with DHL can achieve durable EFS and OS. Using the comprehensive geriatric assessment can aid in decision making in the treatment options for elderly patients. Our retrospective analysis, given a small sample size, suggests that intensive treatment regimens can be offered to elderly patients with DHL.

Safety of BTZ retreatment for patients with low-grade peripheral neuropathy during the initial treatment.

OBJECTIVE: Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment. METHODS: Charts were reviewed from 93 patients who were retreated with a BTZ-containing regimen after previously being treated with this drug. RESULTS: Among the patients who developed PN, most patients in the study had low-grade neuropathy during the initial BTZ treatment (n = 52, 68%). The results showed no evidence of cumulative toxicity, and there was no significant difference in the incidence and severity of PN upon retreatment. Factors such as the presence of baseline PN, number of prior treatments, dose of BTZ, and comorbidities did not increase the severity of PN upon retreatment. The lapse of time between the two regimens also did not affect the severity of PN. CONCLUSION: The results suggest that retreatment with BTZ may be a feasible option, without additional risks of PN, for MM patients even with peripheral neuropathy during their initial treatment with this drug.

Role of sorafenib in overcoming resistance of chemotherapy-failure castration-resistant prostate cancer.

BACKGROUND: Sorafenib promotes apoptosis through downstream pathways that can be deregulated in CRPC. We hypothesized that sorafenib could overcome chemotherapy resistance in CRPC. PATIENTS AND METHODS: Eligible patients were those whose disease had progressed during chemotherapy (docetaxel or mitoxantrone) or within 12 weeks of stopping either. Patients then continued or resumed their last chemotherapy regimen with the addition of sorafenib 400 mg twice daily. Patients received a maximum of 6 cycles of chemotherapy/sorafenib followed by sorafenib alone until disease progression. The primary end point was combination safety. Secondary end points were overall response, percentage of SD, and time to progression (TTP). RESULTS: Twenty-two patients (21 evaluable) were enrolled (16 patients with Gleason score ≥ 7). Median age was 68 years (range, 59-83 years). Median prostate-specific antigen (PSA) was 142 ng/dL (range, 13.6-9584). Visceral and bone disease were present combined in 9 patients (41%). Ten patients (47.6%) showed biochemical response (19% with > 50% PSA decline) and 16 patients (76%) achieved radiographic stability (according to Response Evaluation Criteria for Solid Tumors) after starting sorafenib for a median duration of 6 months (range, 4-12 months). Grade 3/4 nonhematologic toxicities were fatigue (n = 7, 32%), palmar-plantar erythrodysesthesia (n = 4, 18%). Dose reduction of sorafenib occurred at least once in 15 patients (68%) because of palmar-plantar erythrodysesthesia (22%) and fatigue (22%). With a median follow-up of 19 months (range, 3-46 months), median overall survival was 8 months. TTP according to PSA level was 3 months and TTP according to imaging studies and/or clinically was 6 months. Median number of treatment cycles given was 6 (range, 1-10). CONCLUSION: Sorafenib can be combined safely with chemotherapy and in some patients overcomes chemotherapy resistance.

Efficacy and safety of clofarabine in relapsed and/or refractory non-Hodgkin lymphoma, including rituximab-refractory patients.

BACKGROUND: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2) . The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013).

A phase II pilot trial investigating the efficacy and activity of single agent granulocyte macrophage colony-stimulating factor as maintenance approach in castration - resistant prostate cancer patients responding to chemotherapy.

PURPOSE: To investigate the toxicity and efficacy of GM-CSF in castration-resistant prostate cancer (CRPC) patients who maximized their response to systemic chemotherapy. MATERIALS AND METHODS: CRPC patients who maximized their response to either docetaxel or mitoxantrone chemotherapy were eligible if they demonstrated adequate performance status, liver, kidney, and bone marrow function. Maximum response to chemotherapy was defined as either receiving at least 8 cycles of chemotherapy without radiographic or biochemical progression, receiving less than 8 cycles as long as the prostate-specific antigen (PSA) changes by less than 10%, or being off chemotherapy for less than 12 weeks without disease progression. Patients received GM-CSF at 250 mcg/m(2) subcutaneously for 14 days followed by 14 days of rest. GM-CSF was continued until disease progression. RESULTS: Fifteen patients were enrolled of which all were evaluable for toxicity and 13 were evaluable for efficacy. Median age was 78 (range 66-96) and 93% of patients had a Gleason score ≥ 7. Biochemically, 2 patients (15.3%) attained partial response (PR) and 4 (30.7%) had stable disease (SD). Median time to PSA progression was 6 months (range 4-12). Radiographically, 9 patients (69.2%) had SD that lasted a median of 6 months (range 2-10). With a median follow-up of 24 months from starting GM-CSF (range 2-38), 2 patients (13.3%) remain alive and well. Median OS from start of any chemotherapy was 21 months (range 10-44). GM-CSF was well-tolerated with minimal expected manageable toxicities. CONCLUSIONS: GM-CSF is active post-chemotherapy in CRPC patients. Further studies with GM-CSF in this setting are warranted.

A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B cell lymphoma: a report from the CIBMTR.

We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001), and mortality (RR 2.75, 95% CI, 2.03-3.72, P < .001). Risk of disease progression was similar in the 2 groups (RR 1.12, 95% CI, 0.73-1.72, P = .59). In fact, for 1-year survivors, no significant differences were observed for TRM, progression, progression-free (PFS) or overall survival (OS). Increased risks of TRM and mortality were associated with older age (>50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT.