OBJECTIVE: Malignant lymphoma (ML) including Hodgkin\'s lymphoma and non-Hodgkin\'s lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT.
METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events.
RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT.
CONCLUSIONS: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

We report a case of therapy-related myelodysplastic syndrome (MDS), which developed 9 years after autologous peripheral blood stem cell transplantation (PBSCT) for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). A 65-year-old male was diagnosed with PTCL-NOS. After 6 cycles of the CHOP (cyclophosphamide [CPA], doxorubicin, vincristine, and prednisone) regimen, he achieved a first complete response (CR). He relapsed 33 months later and received salvage chemotherapy, which consisted of the CHASE regimen (CPA, high-dose cytarabine, dexamethasone, and etoposide). During the recovery phase of the first cycle of CHASE, his peripheral blood stem cells (PBSCs) were harvested and frozen in 2 bags. After 2 courses of CHASE, he underwent autologous PBSCT, which involved the use of the LEED preconditioning regimen (melphalan, CPA, etoposide, and dexamethasone) and one of the frozen bags. This resulted in a second CR. At 39 months after PBSCT, he relapsed with a tumor in his right arm. After it was resected, he received eight cycles of brentuximab vedotin and 45 Gy of involved-field irradiation concurrently and achieved a third CR. Nine years after autologous PBSCT, he was diagnosed with MDS with excess blasts 2 (MDS-EB-2). His disease progressed to acute myeloid leukemia after 2 courses of azacitidine therapy. He successfully underwent a second autologous PBSCT involving the busulfan and melphalan preconditioning regimen and the other frozen bag, which had been stored for 9 years. He has been in complete cytogenetic remission for 1 year since the second autologous PBSCT.

A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.

Autologous hematopoietic stem cell transplantation (SCT) is not a standard treatment option for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); however, its position has been reassessed since the introduction of tyrosine kinase inhibitors (TKIs). We prospectively analyzed the efficacy and safety of autologous peripheral blood SCT (auto-PBSCT) for Ph+ALL patients aged between 55 and 70 years who had achieved complete molecular remission. Melphalan, cyclophosphamide, etoposide, and dexamethasone were used for conditioning. A total of 12 courses of maintenance therapy, including dasatinib, were performed. The required number of CD34+ cells was harvested in all five patients. No patient died within 100 days after auto-PBSCT, and no unexpected serious adverse events were observed. Although 1-year event-free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389-1088 days) after auto-PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto-PBSCT can be safely performed for Ph+ALL with TKIs. A limitation of auto-PBSCT was suggested, despite the increase in the intensity of a single treatment. The development of long-term therapeutic strategies by including new molecular targeted drugs is warranted to maintain long-term molecular remission.

Autologous stem cell transplantation is routinely used in the management of several hematological diseases, solid tumors, and immune disorders. Peripheral blood stem cell (PBSC) collection performed by apheresis is the preferred source of stem cells. In this study, the potential impact of mobilization regimens on the performance of the Spectra Optia® continuous mononuclear cell collection system was evaluated. We performed a retrospective data analysis for patients undergoing autologous PBSC collection at the Medical University Vienna, Vienna General Hospital between September 2016 and June 2018. Collections were divided into two main groups according to the mobilization regimen received: without (210 collections) or with (99 collections) plerixafor. Assessed variables included product characteristics and collection efficiency (CE). Overall, product characteristics were similar between the groups. Median CD34+ CE2 was 50.1% versus 53.0%, and CE1 was 66.9% versus 69.9% following mobilization without and with plerixafor, respectively; the difference was not statistically significant. Simple linear regression showed a very weak positive correlation between the mobilization method and CE1 or CE2 (mobilization with plerixafor increased CE2 by 4.106%). In conclusion, the Spectra Optia® apheresis system led to high CE and a good quality of PBSC products when mobilization regimens with or without plerixafor were used.

A 54-year-old male patient, who presented with multiple lymphadenopathies, bilateral leg edema, and oscheohydrocele, was diagnosed with diffuse large B-cell lymphoma (DLBCL) stage IVB. His lymphadenopathies disappeared after six courses of R-CHOP therapy, which consist of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone); however, right hypopyon and partly remaining testicular soft tissue masses with fluorodeoxyglucose accumulation were observed. Lymphoma cell infiltration was observed in the aqueous humor of the right anterior chamber and testis, which indicates DLBCL progression. Hypopyon disappeared after the first course of intrathecal chemotherapy combined with R-HDMA therapy, which consists of rituximab and high-dose methotrexate/cytarabine, but recurred in the third course. The patient then underwent busulfan and thiotepa (BuTT) therapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) after four courses of R-HDMA therapy. Hypopyon promptly disappeared after BuTT therapy and no hypopyon recurrence was observed 9 months after auto-PBSCT. Therefore, BuTT therapy is effective for hypopyon associated with refractory DLBCL.

Therapy-related myeloid neoplasms (t-MN) are a leading cause of nonrelapse mortality after autologous peripheral blood stem cell transplantation (aPBSCT) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL). t-MN patients treated at an earlier stage of disease evolution have a better prognosis, and this presents a need to identify patients at risk for t-MN.
Using a prospective longitudinal study design, this study evaluated peripheral blood parameters pre-aPBSCT and on day 100, at 6 months, 1 year, 2 years, and 3 years in 304 patients treated with aPBSCT. The relation between peripheral blood parameters and subsequent development of t-MN was examined, and nomograms were developed to identify patients at risk for t-MN.
Twenty-one patients developed t-MN at a median of 1.95 years post-aPBSCT. Hemoglobin, hematocrit, white blood cell, and platelet counts were lower among patients who developed t-MN compared to those who did not; these differences appeared soon after aPBSCT, persisted, and preceded development of t-MN. Older age at aPBSCT (hazard ratio [HR]per_year_increase = 1.08, P = .007), exposure to total body irradiation (TBI) (HR = 2.90, P = .04), and low 100-day platelet count (HRincrease_per_unit_decline_in_PLT = 1.01, P = .002) predicted subsequent t-MN. These parameters and primary diagnosis allowed identification of patients at high risk of t-MN (eg, an HL patient undergoing aPBSCT at the age of 70 years with TBI and with a day 100 PLT between 100,000 and 150,000 would have a 62% probability of developing t-MN at 6 years post-aPBSCT).
Abnormalities in peripheral blood parameters can identify patients at high risk for t-MN after aPBSCT for HL or NHL, allowing opportunities to personalize close surveillance and possible disease-modifying interventions.

Congestive heart failure (CHF) is a common complication in patients with AL amyloidosis but is rare in another plasma cell dyscrasia, POEMS syndrome. A 52-year-old man developed POEMS syndrome with a solitary plasmacytoma complicated by CHF mimicking cardiac amyloidosis (CA). His neurological symptoms and CHF did not improve after radiotherapy (50 Gy) targeting the plasmacytoma. Based on typical findings of noninvasive examinations such as elevated serum NT-proBNP (12,631 pg/mL), a pseudo-infarct pattern on electrocardiography, interventricular septal thickening with a granular sparkling appearance and an apical sparing pattern of longitudinal strain on echocardiography, and late gadolinium enhancement of the left ventricular wall on cardiac magnetic resonance imaging (MRI), severe CA ineligible for autologous peripheral blood stem cell transplantation (auto-PBSCT) was strongly suspected. However, myocardial biopsy failed to reveal amyloid deposits, and CHF markedly improved after only one cycle of chemotherapy with melphalan and dexamethasone. Accordingly, CA was denied as the etiology of his heart failure, and the patient was finally diagnosed with POEMS syndrome. As a result, high-dose melphalan followed by auto-PBSCT improved his neurological symptoms. Careful evaluation is therefore needed to appropriately treat patients with POEMS syndrome complicated by CHF, even when the results of non-invasive examinations are typical for AL amyloidosis.

Therapeutic practices for multiple myeloma (MM) have evolved, such that novel-agent-based therapy and autologous peripheral blood stem cell transplantation (aPBSCT) is the current standard. Whether cause-specific mortality has changed with time remains unclear. We examined late cause-specific mortality among patients with MM receiving aPBSCT from 1989 to 2014. We conducted a prospective cohort study using participants enrolled in the enrolled in the Blood or Marrow Transplant Survivor Study. We created 3 eras to reflect changing MM therapy: <2000 (pre-thalidomide); 2000-2005 (thalidomide); 2006-2014 (lenalidomide). We used Kaplan-Meier techniques and Cox regression for examining all-cause mortality, and subdistribution hazards models for cause-specific mortality. In total, 1906 patients were followed up for a median of 9.2 years. Conditional on surviving 2 years, the 10-year overall survival was 45%. The 10-year cumulative incidence of myeloma- and non-myeloma-related mortality was 33% and 13%, respectively. Multivariable analysis showed declining MM-specific mortality (subdistribution hazard ratio [SHR]2000-2005 = 0.80, 95% confidence interval [CI], 0.60-1.07; SHR2006-2014 = 0.46, 95% CI, 0.34-0.62; referent group: <2000), infection-related mortality (SHR2000-2005 = 0.50, 95% CI, 0.29-0.85; SHR2006-2014 = 0.35, 95%CI 0.21-0.60; referent group: <2000) and cardiovascular disease-related mortality (SHR2000-2005 = 0.45, 95% CI 0.20-0.99; SHR2006-2014 = 0.41, 95% CI 0.18-0.93; referent group: <2000). Although primary disease remains the major cause of late mortality, we observed a significant temporal decline in myeloma-, infection-, and cardiac-related late mortality over the past 25 years.