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Salvage autologous hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with relapsed multiple myeloma (MM). Peripheral blood stem cells (PBSCs), a source of hematopoietic stem cells (HSCs), are collected before the first transplantation, and adequate quantities of PBSCs can be collected and stored potentially for years to support at least 2 transplantations for eligible patients. To ensure the safety of salvage HSCT in the treatment of patients in subsequent relapse, PBSCs must retain the potential to engraft even after several years of cryopreservation. Although PBSC viability has been studied extensively using in vitro techniques, few publications describe the most rigorous functional potency measure, of patients receiving a myeloablative conditioning regimen. This study describes a large single-institution experience evaluating the engraftment kinetics of PBSCs used in salvage transplantation after multiple years of storage compared with first transplantation for the same patients in the treatment of MM. A retrospective chart review of patients with MM undergoing HSCT between 2000 and 2021 identified 89 patients who received salvage autologous PBSCs stored for >1 year after first HSCT. PBSCs were cryopreserved and stored in vapor-phase liquid nitrogen refrigerators at ≤-150°C. All patients received a PBSC product from the same collection cycle for both transplantations. Differences in CD34 + cell doses and days to engraftment between the first and salvage transplantations were tested using the paired 2-tailed t-test and Wilcoxon signed-rank test. Univariate and multivariable linear regressions were used to determine the association between storage time and days to engraftment, adjusting for CD34 + cell dose and conditioning regimen in the multivariable model. The median duration of storage between the day of initial collection and salvage transplant was 5.4 years (range, 1.0 to 19.7 years). Engraftment kinetics demonstrated a sustained neutrophil engraftment (absolute neutrophil count >0.5 × 10 9 cells/L) at a median of 11 days after both the first and salvage transplantations (range, 8 to 15 days and 8 to 19 days, respectively; P < .05). The median time to sustained platelet engraftment (>20 × 10 9 cells/L without transfusion support) was 13.5 days after the first HSCT and 14 days after salvage HSCT (range, 9 to 27 days and 10 to 56 days, respectively; P = .616). After adjusting for CD34 + cell doses and conditioning regimens, there was no association between the duration of cryopreservation and days to neutrophil engraftment (r = 0.178, P = .130) or platelet engraftment (r = 0.244, P = .100). Engraftment kinetics of the salvage HSCT are comparable to those of the first HSCT even when products are stored in vapor-phase nitrogen refrigerators for a median of 5.4 years. There is no association between the duration of storage and time to engraftment when controlling for CD34 + cell dose and conditioning regimen. Prolonged storage of cryopreserved HSC products is a safe practice for MM patients undergoing salvage autologous HSCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes., Competing Interests: The authors have declared that no competing interests exist.

Autologous hematopoietic stem cell transplantation (ASCT) is a standard-of-care treatment for many hematologic malignancies. Progression of disease after ASCT is the primary cause of treatment failure. In this Phase Ib trial, we studied the safety and clinical effect of combined checkpoint inhibition therapy (CPIT) with ipilimumab and nivolumab as a consolidation strategy after ASCT for patients with high-risk diffuse large B cell lymphoma (DLBCL), mature T cell lymphoma (TCL), and multiple myeloma (MM). Starting at 14 to 28 days after ASCT, patients received ipilimumab (1 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 16, and 22) and nivolumab (3 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, and 26). Patients received a median of 5 doses of ipilimumab and 8 doses of nivolumab. Thirty-five patients were included in the intent-to-treat population. Ninety-four percent of the patients experienced immune-related adverse events (irAEs) of any grade. Ninety-seven percent of irAEs resolved spontaneously or after holding study drugs and instituting high-dose corticosteroid therapy. Progression-free and overall survival at 18 months post-ASCT for each disease cohort were 85.7% and 100% for primary refractory DLBCL, 28.6% and 57.1% for relapsed DLBCL, not evaluable and 80% for frontline TCL, 25% and 75% for relapsed TCL, 57.1% and 87% for high-risk transplant-naïve MM, and 40% and 100% for MM relapsed within 3 years of first ASCT. We conclude that combined CPIT appears to be tolerable as a consolidation strategy after ASCT and in addition to the potential clinical efficacy observed in some subsets of disease, T cell receptor repertoire, T regulatory cell phenotype, and gut microbiota profiles provide a biologic rationale warranting further study of this approach., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.

A regimen of escalating doses of thalidomide, in combination with bortezomib and high-dose melphalan (mel/vel/thal), was evaluated as a conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with a prior transplant who had relapsed or achieved less than a complete remission following a prior ASCT. Thalidomide was dose escalated starting from 600 mg to 1000 mg on days -5 to -1 in a 3 × 3 design, bortezomib was administered at 1.6 mg/m 2 intravenously on days -4 and -1 and melphalan 200 mg/m 2 was administered on day -2. No dose-limiting toxicity was seen in the phase I portion of the trial. An additional 20 patients were enrolled at the maximum tolerated dose of thalidomide of 1000 mg daily. The overall response rate was 69% with 38% complete remission. Median PFS and OS were 9.3 and 65.4 months, respectively, with a median follow-up of 17.8 months. The most common grade 3-4 adverse events (AEs) were neutropenic fever (58.6%), mucositis (6.9%), and diarrhea (6.9%). Serious AEs included somnolence (13.8%) and tumor lysis syndrome (3.4%). The addition of high-dose thalidomide to bortezomib and melphalan as conditioning for salvage ASCT was well tolerated and was an effective conditioning regimen.

Vitamin B12 deficiency is one of the most serious complications of vegetarianism and its variants. Infants born to vegan mothers are at greater risk of serious deficiency, being more vulnerable to their effects. B12 deficiency is not usually suspected by the pediatrician in healthy infants with neurological symptoms. The manifestations are nonspecific: apathy, rejection of food and loss of maturational patterns. A nutritional history of the mother, mainly if she is vegetarian, to estimate her reserves is fundamental to detect risk of deficiency of this vitamin in the small child. The objective of this work is to describe a group of infants, children of vegan mothers, with B12 deficiency and serious neurological compromise: central apneas, seizures, hypotonia, loss of connection with the environment and maturational patterns. Our purpose is to alert about the importance of supplying vegan mothers with B12 before conception until the end of breastfeeding., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535., (© 2019 by The American Society of Hematology.)

Escalating doses of bortezomib with high-dose melphalan was evaluated as as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory multiple myeloma (MM). MM patients with less than a partial remission (PR) (or 50% reduction) compared to their pretransplantation paraprotein parameters after a prior ASCT with melphalan conditioning, or who were in relapse after a prior autologous transplantation, were eligible for study. Bortezomib was dose escalated in steps of 1, 1.3, and 1.6 mg/m 2 (3 × 3 design) on days -4 and -1 before transplantation with melphalan 200 mg/m 2 given on day -2. Thirty-two patients were enrolled: 12 in the phase I dose escalation phase and an additional 20 in phase II to gain additional experience with the regimen. Twenty-four (75%) patients were Durie Salmon stage III, and 12 (37.5%) had >2 prior lines of therapy. The overall response rate (≥PR) was 44% with 22% complete remission. Two-year overall survival and progression-free survival were 76% and 39%, respectively, with a median follow-up of 31.7 months. The most common grade 3 and 4 nonhematologic adverse events were neutropenic fever (25%), nausea (18.8%), and mucositis (9.4%). Serious adverse events included intensive care unit admission (9.4%), seizure (3.1%), prolonged diarrhea (3.1%), and Guillain-Barre syndrome (3.1%). Two patients (6%) died of sepsis. There was no emergent peripheral neuropathy nor increase in any pre-existing peripheral neuropathy. The addition of bortezomib to melphalan as conditioning for salvage ASCT was well tolerated. More importantly, it can provide durable remission for patients who have a suboptimal response to prior single-agent melphalan conditioning for ASCT, without requiring a reduction in the dose of melphalan. Larger randomized prospective studies to determine the effect of combination conditioning are being conducted., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Most patients eligible for allogeneic hematopoietic stem cell transplantation will require identification of an alternate (unrelated or mismatched related) donor. We explored the transplantation outcomes for a sequential series of 54 patients undergoing haploidentical donor transplantation (HAPLO) compared to those from a control group of patients receiving cells from matched or mismatched unrelated donors (URD) selected by diagnosis and stem cell source. Patients undergoing HAPLO transplantations received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (Cy). Day 15 neutrophil recovery was lower after HAPLO than in URD recipients (43% versus 77%, P < .001), as was day 30 platelet recovery (67% versus 84%, P = .043). HAPLO patients receiving bone marrow achieved neutrophil engraftment at a median of 17 days and platelet engraftment at a median of 29 days, compared with 16 days and 24 days, respectively, for recipients of peripheral blood stem cells. The incidence of graft failure was similar for both HAPLO and URD recipients (P = .42). HAPLO recipients were more likely to reach donor CD3 chimerism >95% by day 28 after transplantation (88% versus 62%, P = .003). The cumulative incidence of grades II to IV acute GVHD (aGVHD) at 6 months after transplantation did not differ for these 2 groups (63% for HAPLO and 53% for URD recipients; P = .269), nor did the cumulative incidence of severe grade III/IV aGVHD (13% for HAPLO and 8% for URD recipients; P = .44). The cumulative incidence of moderate or severe chronic GVHD at 2 years did not differ, with probabilities of 24% for HAPLO and 18% for URD recipients (P = .43). The cumulative incidence of cytomegalovirus reactivation by day 100 after transplantation did not differ (45% for HAPLO and 46% for URD recipients; P = .96). The HAPLO recipients experienced a lower incidence of Epstein-Barr virus reactivation by day 100 (6% versus 32%, P < .001) but a higher incidence of Human Herpesvirus-6 reactivation (35% versus 10%, P = .001). Relapse risk, regimen-related mortality, progression-free survival, and overall survival probabilities did not differ between these 2 groups. These data support the use of HAPLO transplantation with post-transplantation Cy as an alternate transplantation technique for patients lacking HLA-matched sibling donors. Transplantation of peripheral blood stem cells does not appear to enhance the speed of neutrophil recovery. The different patterns of viral reactivation require additional studies to explain., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We conducted a study of patients with multiple myeloma (MM) undergoing allogeneic transplantation to evaluate outcome parameters. Fifty-seven consecutive patients with MM received an allogeneic transplantation between 2004 and 2011 at our institution. Patients who had received at least 1 prior autologous transplantation were included. Twenty-six patients underwent allogeneic transplantation for consolidation after a response to their first autograft, and 30 patients received an allogeneic transplantation as salvage therapy. Donor source was evenly distributed between related and unrelated. The median follow-up was 52 months. Thirty-two (57.1%) patients achieved a complete response (CR). At 5 years, 49.2% of all patients were in CR. Sixteen patients received either donor lymphocyte infusions or immune suppression withdrawal for disease progression, with a 62.5% response rate. The 5-year overall survival (OS) for all patients was 59%. The 5-year OS for the 30 patients in the consolidation group was 82% compared with 38% for those in the salvage group. In multivariate analysis, 3 factors remained significantly associated with OS. These include being in the salvage group (hazard ratio [HR], 4.05; P = .0196), acute graft-versus-host disease (aGVHD) (HR, 2.99; P = .034), and chronic graft-versus-host disease (cGVHD), which was highly protective, with a 5-year OS of 78.8% for patients with cGVHD versus 42.6% for patients without cGVHD (HR .17, P = .008). Our data show that allogeneic transplantation for MM can lead to sustained remissions. aGVHD is significantly deleterious to OS and progression-free survival, whereas cGVHD is strongly favorable, supporting an important role for the graft-versus-myeloma effect., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. We conducted a Phase I/II trial of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose-escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER, patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] followed by autologous stem cell transplantation (autoSCT). Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4 haematological toxicities resolved appropriately, and planned dose density and dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions were required in any of the three cycles. After two cycles of RICER, nine of 15 patients (60%) achieved a complete response, and two achieved a partial response (13%). Combining lenalidomide with RICE is feasible, and results in promising response rates (particularly complete response rates) in high-risk DLBCL patients., (© 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

Transplantation of hematopoietic progenitor cells from red cell-incompatible donors occurs in 30-50% of patients. Immediate and delayed hemolytic transfusion reactions are expected complications of red cell-disparate transplantation and both ABO and other red cell systems such as Kidd and rhesus can be involved. The immunohematological consequences of red cell-incompatible transplantation include delayed red blood cell recovery, pure red cell aplasia and delayed hemolysis from viable lymphocytes carried in the graft ('passenger lymphocytes'). The risks of these reactions, which may be abrupt in onset and fatal, are ameliorated by graft processing and proper blood component support. Red blood cell antigens are expressed on endothelial and epithelial tissues in the body and could serve to increase the risk of GvHD. Mouse models indicate that blood cell antigens may function as minor histocompatibility antigens affecting engraftment. Similar observations have been found in early studies of human transplantation for transfused recipients, although current conditioning and immunosuppressive regimens appear to overcome this affect. No deleterious effects from the use of red cell-incompatible hematopoietic grafts on transplant outcomes, such as granulocyte and platelet engraftments, the incidences of acute or chronic GvHD, relapse risk or OS, have been consistently demonstrated. Most studies, however, include limited number of patients, varying diagnoses and differing treatment regimens, complicating the detection of an effect of ABO-incompatible transplantation. Classification of patients by ABO phenotype ignoring the allelic differences of these antigens also may obscure the effect of red cell-incompatible transplantation on transplant outcomes.

Rituximab, an anti-CD20 human-mouse chimeric monoclonal antibody has been shown to improve response rates when it is combined with standard salvage chemotherapy in patients with relapsed or refractory intermediate-grade B-cell non-Hodgkin's lymphoma. A vast majority of these patients subsequently undergo high-dose therapy followed by stem cell transplantation. However, the impact of rituximab on stem cell mobilization kinetics is not well characterized. The purpose of this study was to study the effect of high-dose rituximab given with chemotherapy on stem cell mobilization in patients with intermediate-grade B-cell non-Hodgkin's lymphoma. Thirty-six patients received ifosfamide, etoposide, and rituximab followed by filgrastim for stem cell mobilization. The chemotherapy regimen was well tolerated. Thirty-four of 36 patients (94%) were able to mobilize at least 2 x 10(6) CD34+ cells/kg body weight after a median of 2 apheresis procedures. The median CD34+ cell dose collected per kilogram of recipient body weight was 6.5 x 10(6) (range, 4.65-31.15). All patients who subsequently underwent high-dose chemotherapy and stem cell transplantation experienced sustained engraftment. In conclusion, high-dose rituximab given during stem cell mobilization does not negatively affect stem cell mobilization kinetics.

The role of high-dose chemotherapy (HDCT) in patients with refractory breast cancer is not well established. Forty-two female patients (median age of 46 years) with breast cancer refractory to neoadjuvant chemotherapy received HDCT (cyclophosphamide, carmustine and thiotepa) supported by an autologous peripheral blood stem cells transplant. Their disease had been refractory (defined as less than partial response) to one (18 patients) or two (24 patients) regimens of neoadjuvant chemotherapy. Twenty-nine patients had surgery before HDCT. The best response after surgery, HDCT, and radiation therapy was assessed 60 days after transplantation. Thirty patients had complete remission, eight had a PR, one had a minor response, and three had progressive disease. In seven of 13 patients whose disease was inoperable before HDCT, it became operable. After a median follow-up of 42 months, 21 patients were alive, and 15 remained disease free. Five-year overall survival (OS) was 57% (CI, 50-64%), and the estimated 5-year progression-free survival was 40% (CI, 32-48%). Both OS and PFS were better in patients whose disease became operable after chemotherapy than in those whose disease remained inoperable. A randomized study is warranted in this patient population.

Scleromyxedema, the most severe manifestation of the spectrum of lichen myxedematosus, is characterized by cutaneous mucinosis, extracutaneous manifestations, and a monoclonal gammopathy. Seven of 8 patients evaluated at our center were treated with high-dose melphalan (180 mg/m(2) intravenously) and autologous peripheral blood stem cell transplantation, with marked improvement of gastrointestinal, central nervous system, pulmonary manifestations, and Karnofsky performance status. Five patients obtained a cutaneous complete remission and 2 patients had partial remissions. Three patients with slight progression in the skin at 12, 8, and 4 months after treatment received a second cycle of high-dose melphalan and had further symptomatic improvement. The lichen myxedematosus-scleromyxedema spectrum appears to be a continuum that requires the presence of a serum paraprotein and differs in severity of skin lesions, extracutaneous manifestations, and performance status. High-dose melphalan followed by autologous transplantation appears effective for improving the symptoms and systemic manifestations of scleromyxedema.

Purpose: We investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkin's lymphoma (NHL)., Patients and Methods: Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m(2) and 7 days after chemotherapy at 1,000 mg/m(2)), together with granulocyte colony-stimulating factor 10 mug/kg and granulocyte-macrophage colony-stimulating factor 250 microg/m(2) administered subcutaneously daily. HD-R of 1,000 mg/m(2) was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab., Results: With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to >/= 500 cells/microL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab., Conclusion: The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Background: Hematopoietic stem cell transplantation (HSCT) is an effective but expensive medical procedure to which some ethnic minorities, the elderly, and those without insurance have been shown to have limited access. The purpose of the current study was to determine whether socioeconomic factors were associated with HSCT usage rates in patients with leukemia., Methods: The authors identified 6574 patients with acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, or other leukemias from the 1999 Texas Hospital Inpatient Discharge Public Use Data File. Of these patients, 1604 received an autologous or allogeneic HSCT. The authors assessed patients' ethnicity, payer status, age, gender, and comorbid medical conditions. Logistic regression was used to control for patient characteristics and to evaluate associations among payer status, ethnicity, and HSCT use. P < or = 0.05 indicated statistical significance., Results: Patients who self-paid had the highest rate of HSCT use in all age groups (32%; P < or = 0.01) and in the adult group (36%; P = 0.11). Elderly patients with Medicare had a low rate of HSCT use (17%; P = 0.13). Logistic regression showed no statistically significant associations between payer status or ethnicity and HSCT use. However, elderly women were significantly less likely to undergo HSCT than elderly men (odds ratio, 0.34; P < or = 0.01)., Conclusions: The lack of statistically significant differences in HSCT use among adult patients with leukemia was surprising because previous studies had shown differences in HSCT by ethnicity and insurance., ((c) 2004 American Cancer Society)

We assessed the 5-year results of a high-dose cyclophosphamide, carmustine, and thiotepa (CBT) regimen plus autologous hematopoietic stem cell transplantation (AHST) as an adjuvant consolidation therapy for high-risk primary breast cancer patients with > or =10 positive axillary lymph nodes after primary surgery or > or =4 positive axillary lymph nodes after neoadjuvant chemotherapy and surgery. The associations of various potential prognostic factors with the relapse-free survival (RFS) rate and overall survival (OS) rate were determined. Between October 1992 and March 2000, 177 eligible patients (median age, 46 years) were given high-dose CBT followed by AHST. At a median follow-up of 63 months, the acute treatment-related mortality was 4.5%. Estimated 5-year RFS and OS rates were 62% and 68%, respectively, for all patients. For patients with > or =10 positive axillary lymph nodes after primary surgery, the 5-year RFS and OS rates were 71% and 70%, respectively, and for patients with > or =4 positive axillary lymph nodes after neoadjuvant chemotherapy, the 5-year RFS and OS rates were 53% and 66%, respectively. In 2-sided log-rank tests, earlier disease stage, a lower lymph node ratio, and a lower tumor score were associated with a prolonged RFS and OS. In a multivariate proportional hazards model, disease stage and lymph node ratio remained significant. We concluded that high-dose CBT with AHST for high-risk primary breast cancer is feasible, with comparable efficacy to other phase II studies. More than a 50% estimated 5-year survival rate was seen in all high-risk primary breast cancer patients. In accordance with results from recent randomized studies, we need to continue high-dose chemotherapy with AHST for patients with high-risk primary breast cancer in the phase III randomized setting.

Invasive fungal infections have emerged as a significant problem in patients with cancer with the development of better systemic therapies for malignancy and more effective antibacterial agents. The currently available world published medical literature was reviewed on invasive fungal infections in cancer patients with specific attention devoted to the multidisciplinary role of surgery in refractory cutaneous cases. Infections can develop on the forearm where peripheral intravenous catheters had been inserted in cancer patients undergoing cytotoxic chemotherapy. Curative intent begins with systemic contemporary anti-fungal therapy. Following resolution of neutropenia, patients may require radical surgical debridement with negative margins of resection for complete eradication of the fungal infection. Although invasive fungal infections refractory to antifungal systemic therapy in immunocompromised patients undergoing chemotherapy are a rare event, it is critical for surgeons and other multidisciplinary clinicians to recognize these potentially life-threatening infections that may necessitate radical surgical resection for cure.

Nine patients with advanced Hodgkin's lymphoma (HL) who had undergone allogeneic stem cell transplantation (allo-SCT) received donor leukocyte infusions (DLIs) for treatment of persistent or progressive disease (PD). A total of 15 DLIs were performed, with four patients receiving more than one DLI. In four patients, prior salvage chemotherapy was administered. The median CD3+ cell dose administered was 77.5 x 10(6)/kg (range 5-285). GVHD developed in all but one patient. The response rate was 4/9 (44%). Three of these four responders developed GVHD and 3/4 had received chemotherapy. No correlation was observed between CD3+ cell dose infused and disease response. At the latest follow-up, three patients are alive and six have expired (PD n=3, nonrelapse mortality n=3). The median response duration was 7 months (range 4-9), with one response currently ongoing. These data suggest that DLIs for immunotherapy of recurrent HL have significant activity, although they frequently leads to GVHD. The small sample size does not allow any conclusion as to whether chemotherapy administration increases the chance of response. The CD3 cell dose infused does not seem to correlate with disease response.

The purpose of this study was to identify characteristics significant to survival and progression-free survival in patients with advanced ovarian cancer receiving high-dose chemotherapy. In all, 96 patients received autologous stem cell transplantation. Regimens included paclitaxel with carboplatin (PC), topotecan, melphalan, cyclophosphamide (TMC) and cyclophosphamide, BCNU, thiotepa (CBT). At the time of transplantation, 43% of patients were in clinical CR, 34% were in clinical PR, 18% had progressive disease and 5% had stable disease. There were no treatment-related deaths. The 6-year survival by Kaplan-Meier was 38%. For patients who received transplantation for remission consolidation, the 6-year survival was 53% with a PFS of 29%. On univariate analysis, the CBT regimen, clear cell histology and disease status other than CR prior to treatment were statistically significant adverse prognostic factors. This analysis has demonstrated that patients in clinical remission are most likely to benefit from autologous transplantation, with the exception of patients with clear cell histology. The TMC combination appeared to be superior to the PC and CBT combinations. Comparative studies of different consolidation approaches will be necessary to determine if autologous transplantation is the preferred treatment for this patient population.

The goal of this trial was to assess the toxicity and potential efficacy of high-dose topotecan, melphalan and cyclophosphamide as a preparative regimen for patients with multiple myeloma undergoing autologous stem cell transplantation. Eighteen patients were treated, 8 for first remission consolidation, 4 with relapse sensitive disease, 3 primary refractory and 3 relapsed refractory. The median age was 56 (38 - 65) and the median number of prior regimens was 3 (1 - 8). Patients received cyclophosphamide 1 g/m2/d on days -6, -5, -4; melphalan 70 mg/m2 on days -3, -2 and topotecan 3.0 to 3.5 mg/m2/d on days -6 to -2. Peripheral blood stem cells were infused on day 0. Toxicity (Bearman Toxicity Criteria) was mostly limited to grade 1 - 2 mucositis and grade 1 diarrhea. There were no transplant-related deaths. The overall response rate at 3 months post transplantation was 89% with 17% CR, 2 of those in refractory patients. The overall response rate in refractory patients was 67%. With a median follow up of 12.3 months, 89% of patients are alive. The TMC regimen is well tolerated and produces high response rates. Further evaluation of TMC to fully assess response and survival is ongoing.

Background: We are reporting on a case of platinum-refractory low-grade ovarian cancer responding to treatment with an allogeneic bone marrow transplantation from an unrelated donor., Case: The 37-year-old patient received a preparative regimen consisting of fludarabine 25 mg/m(2) on days -6, -5, -4, -3 and -2, melphalan 70 mg/m(2) on days -3 and -2, and thymoglobulin 2 mg/kg on days -3, -2 and -1. An unrelated HLA-compatible bone marrow was infused on day 0. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. The patient demonstrated complete donor chimerism. Serial CT scans of the abdomen and pelvis over the following 15 months showed a slow regression of the malignant lesion., Conclusion: Engraftment of an unrelated donor marrow was achieved in a patient with ovarian cancer and induced a tumor response. This suggests the presence of a graft-versus-tumor effect in ovarian cancer. Further study is underway.

The aim of this study was to study the effectiveness of the Swenerton score in assessing extent of disease as an independent prognostic and predictive factor in patients with metastatic breast cancer (MBC) who receive high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplant (AHSCT). Two-hundred thirty-two patients with MBC underwent HDCT. Extent of disease was assessed quantitatively using the Swenerton score. A retrospective analysis was performed using Cox proportional hazards regression and logistic regression models. One hundred three (44%) patients had a complete response (CR) after HDCT. Bone marrow as source of hematopoietic stem cells, hormone-receptor-negative status, and visceral involvement correlated with both worse overall survival (OS) and progression-free survival (PFS). Short disease-free interval, multiple sites of metastatic disease, and less than 50% reduction in the Swenerton Score during induction chemotherapy correlated with worse OS. Patients in CR at the time of HDCT had better PFS than patients in partial response, stable disease, or progressive disease. Fifty-six patients who underwent conversion to CR after HDCT had a similar median OS (not reached v 74 months; P =.51) and PFS duration (22 v 44 months; P =.15) as patients who received HDCT after a CR to standard-dose chemotherapy (SDCT). Conversion to CR was predicted by a >/=50% reduction in the Swenerton score during SDCT (odds ratio [OR] 3.32, P <.01) and soft-tissue disease (OR 4.08, P <.01). The presence of multiple metastatic sites predicted decreased probability of conversion to CR (OR 0.34, P <.01). The Swenerton score provides a thorough estimate of disease extent, and reduction of Swenerton score by SDCT is potentially useful for selecting the optimal candidates for HDCT trials who may achieve long-term disease control.

Objective: The goals of this study were to: (1) systematically evaluate patient preferences regarding side effects of high-dose chemotherapy with stem cell support for treatment of advanced ovarian cancer; and (2) assess whether patients' preferences changed over time., Methods: Forty patients with stage III or IV disease were enrolled in this study. Patients' preferences regarding 12 health states (side effects) were assessed using visual analogue scale (VAS) and time trade-off (TTO) methods during mobilization chemotherapy (T(1)) and 6-7 weeks later after high-dose chemotherapy and stem cell transplant (T(2)). Each assessment involved a 45-min interview conducted at the patient's bedside., Results: The three most preferred health states were no evidence of disease (NED), a chemotherapy with few or no side effects, and alopecia, while the least preferred health states were chemotherapy with multiple severe side effects, hepatotoxicity, and nausea and vomiting. These results were observed at both T(1) and T(2) using both preference assessment methods. Pancytopenia scores significantly increased from T(1) to T(2) using the VAS method (P < 0.05), but decreased using the TTO method., Conclusions: Chemotherapy-experienced women with ovarian cancer have consistent preferences for the best and worst health states associated with the side effects of chemotherapy. Patients are more averse to nausea and vomiting than many other symptoms. Women's perceptions of pancytopenia may be dependent upon the number of prior cycles of chemotherapy and site of care for anemia, thrombocytopenia, and febrile neutropenia.

This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 microg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 microg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached > or = 2 x 10(9)/L; leukapheresis was continued until acquisition of a target dose of > or = 5 x 10(6) CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 x 10(6) CD34 cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 x 10(6) cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after high-dose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 x 10(9)/L and a platelet count of 20 x 10(9)/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.

This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 days or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.

Objective: The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer., Methods: Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0., Results: The optimal topotecan dose selected for future trials was 4.0 mg/m(2)/day x 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive., Conclusion: With a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer., (Copyright 2001 Academic Press.)

Objective: To evaluate the antitumor activity and toxic effects of intensive-dose ifosfamide plus etoposide with filgrastim given as stem cell mobilization therapy before high-dose chemotherapy for recurrent or persistent ovarian cancer., Methods: We studied 32 patients with epithelial ovarian cancer who had a positive second-look laparatomy or recurrent disease. Ifosfamide was given at 10 g/m2 (total dose) by continuous infusion over 72 h; etoposide was given at 150 mg/m2 in 2-h infusions every 12 h during the same 72-h period; and filgrastim was given at 10 microg/kg/day subcutaneous injection from day 5 through completion of stem cell harvest., Results: Nine (64%) of the 14 patients assessed responded to the treatment. The target stem cell dose was achieved with a median of 1 apheresis (range 1-5 aphereses). Nonhematologic toxicity was limited to grade 2 nephrotoxicity in one patient and grade 2 hepatic toxicity in three patients., Conclusions: In this patient group, intensive-dose ifosfamide plus etoposide with filgrastim was well tolerated and produced antitumor activity.

We studied 36 patients with non-Hodgkin's lymphoma to evaluate the stem cell yield following recovery from intensive dose ifosfamide and etoposide given as mobilization chemotherapy. We also assessed the toxicity of the regimen and engraftment kinetics. All patients had intermediate grade lymphoma and had either failed to achieve a complete remission to induction chemotherapy or had relapsed. Patients received ifosfamide 10 g/m2 IV total dose given over 72 hours, etoposide 150 mg/m2 IV every 12 hours for 6 doses and G-CSF 10 microg/kg/d. Thirty-four patients went on to receive high-dose chemotherapy with BEAM or with CVP and BEAM. A median of 2 (1-10) apheresis was required to reach the target CD34+ count of >4 x 10(6)/kg. A median of 13.1 CD34+ cells/kg (4.1-148) was obtained. Toxicity was limited to mucositis in 3 patients, transient confusion and transient rise in liver function tests in 3 and 2 patients respectively. The median time to engraftment was 10 days (8-17) for all the patients undergoing high-dose chemotherapy. The regimen of intensive dose ifosfamide and etoposide along with G-CSF is well tolerated and in this group of patients has lead to successful stem cell harvests and sustained engraftment.