Autologous peripheral blood stem cell transplantation (PBSCT) for Hodgkin lymphoma (HL) is curative for many patients with relapsed or refractory disease. Relapsing disease, however, remains a major ...problem. Neoplastic transformation of B-lymphocytes probably underlies the development of classical HL. Whether clonal B cells are critical for disease evolution and response to therapy in HL remains uncertain. We investigated the impact of clonal B cells detected in peripheral blood stem cell (PBSC) collections on the outcome of patients with HL undergoing transplant. Qualitative semi-nested PCR was carried out on genomic DNA from mononuclear cells from PBSCs to determine the presence of clonal immunoglobulin heavy chain (IgH) complementary-determining region 3 (CDR3) gene rearrangements. Clinical factors were assessed for their association with relapse, overall survival (OS) and progression-free survival (PFS). Among 39 patients undergoing PBSCT, 12 grafts (31%) were PCR positive for clonal IgH rearrangements. OS was better in the PCR-negative group (logrank test, P=0.041). The OS at 5 years was 81% in PCR-negative versus 39% in PCR-positive patients; hazard ratio was 3.23 (95% confidence interval: 0.98-10.63). There was a trend towards better PFS (logrank test, P=0.12), estimated as 71% at 5 years in PCR-negative versus 41% in PCR-positive patients. Clonal B-lymphocytes in PBSC collections of patients with HL identify patients at risk of poor outcome. Larger series are needed to confirm our observations. Insight regarding the role of monoclonal B cells may lead to improved therapies.
The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) ...transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients < or =70 kg received 300 microg/day and >70 kg 480 microg/day. All patients were reinfused with PBPCs with a CD34+ cell count >2.0 x 10(6)/kg. Baseline characteristics of age, sex and CD34+ cell count were similar between the two arms, the median CD34+ cell count being 5.87 x 10(6)/kg in the day +1 group and 7.70 x 10(6)/kg in the day +7 group (P=0.7). The median time to reach a neutrophil count of >0.5 x 10(9)/l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P=0.68). Similarly, there was no difference in median days to platelet recovery >20000 x 10(9)/l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P=0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P=0.7), intravenous antibiotic use (7 vs 8 days; P=0.54) or median number of red blood cell transfusions (4 vs 7 units; P=0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P < 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug costs. For patients with an adequately mobilized PBPC graft, the initiation of G-CSF can be delayed until day +7 post-PBPC reinfusion.
Objective
To assess demyelination and remyelination in vivo in acute gadolinium (Gd)‐enhancing lesions of multiple sclerosis (MS).
Methods
We measured significant changes in magnetization transfer ...ratio (MTR) consistent with demyelination and remyelination of individual lesion voxels, as well as the mean normalized MTR over all lesion voxels during and after contrast enhancement, in MS patients participating in a 3‐year Canadian trial assessing immunoablation and autologous stem cell transplantation for treatment of MS.
Results
The average mean normalized lesion MTR over all lesions exhibited partial recovery over 2 to 4 months after Gd enhancement. Voxel‐based analysis demonstrated that approximately 70% of the initially enhancing lesion volume (GdLV) was left with stably low MTR over 39 months of evaluation. The percentage of the GdLV undergoing significant increases in MTR consistent with remyelination increased for approximately 7 months after enhancement and then stabilized at 21 %GdLV. Significant decreases in MTR consistent with demyelination were ongoing for approximately 33 months after enhancement, stabilizing at 9 %GdLV. The estimated error of these measurements, based on scan/rescan analysis, was less than 0.4 %GdLV.
Interpretation
We found significant changes in MTR consistent with demyelination and remyelination that followed different temporal evolutions and were ongoing in different lesion regions for at least 3 years after lesion formation. Ann Neurol 2008
Imatinib, an inhibitor of the mutant tyrosine kinase that causes chronic myeloid leukemia (CML), is effective in patients with chronic-phase CML who have no response to the standard treatment, ...interferon alfa. In this study of 1106 patients with previously untreated chronic-phase CML, imatinib was superior to a combination of interferon alfa and cytarabine as initial therapy.
In a study of 1106 patients, imatinib was superior to interferon alfa plus cytarabine as initial therapy.
The Philadelphia chromosome (Ph),
1
the result of a t(9;22) reciprocal translocation,
2
is present in over 90 percent of patients with chronic myeloid leukemia (CML) and results in the juxtaposition of DNA sequences from the
BCR
and
ABL
genes.
3
–
6
BCR-ABL
encodes a protein, p210BCR-ABL, with dysregulated tyrosine kinase activity,
7
which is necessary and sufficient for leukemogenesis.
8
–
11
Imatinib mesylate (Gleevec, Novartis), a potent competitive inhibitor of the tyrosine kinases associated with ABL,
12
,
13
C-KIT,
14
,
15
platelet-derived growth factor receptor,
13
,
14
,
16
and ARG,
17
impedes the interaction of ATP with these proteins
18
and thereby inhibits their ability to phosphorylate and activate . . .
Outpatient total body irradiation (TBI) as part of a comprehensive outpatient transplant program was delivered to 142 of 167 (85%) consecutive patients receiving TBI-based conditioning therapy. ...Outpatients received either a single fraction of 500 cGy (110 patients) or 1200 cGy in six fractions over 3 days (32 patients). Patients were assessed daily and were administered oral ondansetron and dexamethasone for prophylaxis of nausea and vomiting as well as i.v. hydration. Accommodation during outpatient TBI-based conditioning was either the patient's home if within 30 min of the hospital, a hotel on the hospital grounds or on a closed hospital ward. None of the 142 patients required admission to the inpatient program during their TBI. There was no difference in 100-day mortality between those receiving TBI as an outpatient (9%) vs as an inpatient (16%). Of four deaths occurring within the first 14 days post transplant, none could be attributed to receiving TBI as an outpatient. Two hundred and six inpatient days were saved through the delivery of outpatient TBI. A comprehensive outpatient program, appropriate patient selection, daily hydration, the use of prophylactic 5HT3 antagonist anti-emetic therapy all contribute to the safe delivery of outpatient TBI.
Background:
Primary central nervous system lymphoma (PCNSL) is a rare malignancy with a median survival of less than 3 months, if untreated. Multimodality treatments with high‐dose methotrexate ...(HD‐MTX)‐based systemic therapy and/or whole brain irradiation for consolidation or salvage constitutes the most commonly used treatment approach. Due to severe treatment toxicity and aggressive course of the disease, not all patients benefit from this treatment approach.
Aims:
In this retrospective study, we aimed to identify various clinical parameters that predicted outcomes on survival, and response to various treatments in patients with PCNSL.
Methods:
Patients diagnosed with PCNSL between 2002 and 2017 were selected for analysis. Data on patient demographics, tumor characteristics and treatment were collected and analyzed for correlation with clinical outcomes. Survival curves were generated with the Kaplan‐Meier method and compared using log‐rank test. Multivariate analysis was performed where prognostic variables and patient outcome were correlated with Cox proportional hazard model.
Results:
A total of 82 patients were identified and selected for analysis. Median age at diagnosis was 68 years (range 30‐89 years) and median follow up was 3.7 years. The majority (86.6%) of tumors were identified as diffuse large B‐cell lymphoma on histology. Among the 82 patients, 10 (12.2%), 31 (37.8%) and 23 (28.0%) patients received systemic therapy (CT) only, radiotherapy (RT) only and systemic therapy followed by salvage radiotherapy (CRT), respectively, while 18 (22.0%) patients received supportive care (SC) only. Median time interval between diagnosis and treatment was 33 days for CT group and 63 days for RT group. Median overall survival (OS) of the entire cohort was 11.1 months (95% CI 6.1‐15.5 months), while median OS for RT, CRT and SC groups were 8.8 months (95% CI 4.5‐11.3 months), 30.1 months (95% CI 19.3‐41.0 months) and 3.3 months (95% CI 0.8‐5.8 months), respectively (median OS for CT group not reached). Multivariate analysis demonstrated that both the use of systemic therapy (hazard ratio HR 0.23, 95% CI 0.11‐0.49, p < 0.001) and radiotherapy (HR 0.54, 95% CI 0.32‐0.92, p = 0.022) were associated with improved survival in the total population, while age (p = 0.48) or type of tumor (p = 0.88) did not demonstrate any statistical significance. Subgroup analysis showed that systemic therapy in patients younger than 70 years of age was associated with improved OS (HR 0.13, 95% CI 0.05‐0.32, p < 0.001), whereas in elderly patient population (70 years of age or older), addition of radiotherapy was associated with improved OS (HR 0.45, 95% CI 0.21‐0.96, p = 0.039).
Summary/Conclusion:
Our results concur with the published literature demonstrating the survival benefit with the use of systemic therapy in younger patient population. Radiotherapy was independently associated with an improved overall survival in older patient population and therefore should be considered as palliative treatment of choice in the elderly population who may not be candidates for systemic therapy. Further prospective studies are required to validate our findings as well as optimization of radiotherapy in this population.
Increasingly, PBPC instead of BM are used for autologous transplantation. Limited data exist on the economic effects of this change. Using a resource-based utilization model we prospectively ...determined the costs of 48 autologous transplants (eight BM, 17 BM + PBPC, 23 PBPC), isolating the post-reinfusion period (day 0 to discharge) to better determine the effect of the rescue product. Length of stay post-reinfusion was significantly shorter in patients receiving PBPC (median 13 days) or BM + PBPC (median 14 days) vs BM alone (median 20 days) (P < 0.01). Accordingly, transplant admission costs were less in the PBPC groups (PBPC $22089, BM + PBPC $23179) vs the BM alone group ($32289) (P < 0.05). Rescue product acquisition costs were higher for PBPC (range $3439-$5157) vs BM ($2766) but these costs were offset by the more rapid recovery of patients receiving PBPC. Overall transplant costs depend on the conditioning regimen with a 10-fold cost variation among regimens. Modeled costs for autologus transplantation using various approaches to rescue product acquisition are given. The introduction of PBPC for autologus transplantation has resulted in cost savings at our institution. Although the acquisition costs of PBPC rescue product are greater than for BM, this incremental expense is more than offset by a less expensive post-reinfusion period.
To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never ...achieve a complete remission with conventional chemotherapy.
Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America.
Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval CI, 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival.
High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.
Multiple sclerosis (MS) lesions show differing degrees of demyelination and remyelination. Changes in myelin content are associated with changes in magnetization transfer on MRI. Since acute ...inflammation and demyelination are spatially and temporally inhomogeneous, we hypothesized that local magnetic transfer ratio (MTR) heterogeneity might be predictive of subsequent changes in MTR. To test this hypothesis, we analyzed MTR images obtained in 14 subjects, at baseline and after 2 months follow-up. We segmented lesions and normal-appearing white-matter (NAWM), calculated MTR signal inhomogeneity maps at baseline and MTR lesion difference maps between baseline and follow-up. We found that regions with low MTR inhomogeneity at baseline experienced little further change in MTR on follow-up. The mean change in lesion MTR between baseline and follow-up was 0.10 ± 3.70; in NAWM it was −0.09 ± 2.02. We found that regions with high MTR inhomogeneity at baseline would change MTR on follow-up: (1) voxels with significantly high MTR in regions of high MTR inhomogeneity at baseline showed a mean decrease in MTR between baseline and follow-up of −2.51 ± 4.68 in lesions and −1.41 ± 3.00 in NAWM; (2) voxels with low MTR in regions of high MTR inhomogeneity at baseline showed a mean increase in MTR between baseline and follow-up of 2.61 ± 6.07 in lesions. These changes in MTR were significantly different (
P < 0.001). These results suggest that calculation of MTR signal inhomogeneity may provide a method for quantifying the potential for remyelination and demyelination, and thus could provide an important MRI biomarker for assessing the efficacy of therapies targeting remyelination.
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