Clinical Lymphoma and Myeloma最新文献

Granulomatous slack skin (GSS) is an extremely rare subtype of cutaneous T-cell lymphoma. A 14-year-old boy had suffered from progressive infiltrative erythema and plaques that gradually evolved into lax masses and pendulous skin on his axilla, anterior wall of the abdomen, bilateral inguinal region, and thighs. Histopathologic examination of the skin lesion and inguinal lymph node demonstrated granulomatous infiltration with multinucleated giant cells. Positron emission tomography (PET)/computed tomography (CT) scan was performed after acute exacerbation and exhibited slightly high fluorodeoxyglucose (FDG) distribution of skin lesions, without any evidence of abnormality in the metabolism of FDG in lymph nodes or other extralymphatic organs. Concurrent use of corticosteroid and recombinant interferon-α successfully controlled the disease, and posttreatment PET/CT scan confirmed the response to the therapy with decreased levels of FDG uptake. PET/CT is suggested to be helpful in the assessment of disease progression and treatment response in the management of patients with GSS.

Purpose

In this study, we sought to evaluate the efficacy and toxicity of high-dose therapy followed by autologous peripheral blood stem cell transplantation (autoPBSCT) after rituximab-containing induction chemotherapy with in vivo purging for relapsed or refractory chemosensitive advanced-stage follicular lymphoma (FL).

Patients and Methods

A rituximab-containing regimen was used as induction chemotherapy and as in vivo purging before PBSC collection. Patients achieving partial or complete response received a regimen consisting of high-dose melphalan and total-body irradiation (TBI).

Results

A total of 18 patients with a median age of 45 years were enrolled. The number of previous chemotherapy regimens was 2. The principal nonhematologic toxicities were grade 3 febrile neutropenia and diarrhea. One patient experienced pneumocystis pneumonia, 2 developed interstitial pneumonitis, and 1 experienced agammaglobulinemia, all of whom had complete improvement except for the patient having agammaglobulinemia. Grade 4 toxicities were not observed, and there have been neither treatment-related mortality nor secondary malignancy to date. At a median follow-up of 4.0 years, the 4-year estimated overall and failure-free survival rates were 100% and 88.9%, respectively.

Conclusion

Consolidation of high-dose melphalan and TBI followed by autoPBSCT with in vivo purging is feasible and effective for relapsed or refractory chemosensitive FL. Longer follow-up is needed to confirm the role and late toxicities.

The molecular monitoring of chronic myeloid leukemia allows the clinician a minimally invasive method to judge response to tyrosine kinase therapy and to predict outcome and relapse. Because there are several treatment options for patients with suboptimal response, the ability to proactively predict and respond to relapse makes the “personalization” of treatment a realizable goal. There are practical issues with molecular monitoring, however, including availability of assays, standardization of tests, and the learning curve as doctors and patients learn to follow BCR-ABL levels with interest and reason. This review will examine the use of molecular monitoring in the non-trial setting, concentrating on pitfalls that can occur in the real-world delivery of complex medical care.

Purpose

We evaluate the effectiveness and toxicity of high-dose sequential chemotherapy (HDS) as salvage therapy in patients with advanced-stage Hodgkin lymphoma.

Patients and Methods

We performed a retrospective analysis on 77 patients receiving HDS between 1998 and 2006. Patients enrolled were in disease progression or relapsed disease, or did not achieve a complete remission after first-line treatment. HDS consisted of the sequential administration of cyclophosphamide and granulocyte colony-stimulating factor with stem cell harvesting, followed by methotrexate plus vincristine and etoposide.

Results

The majority of patients had stage III/IV (64%) and B symptoms (71.4%). Disease status improvement after HDS was observed in 24 of 57 patients (42%) previously in disease progression or relapse. HDS-related deaths occurred in 8 of 77 patients (10.4%). Four patients (5.2%) developed acute myeloid leukemia/myelodysplastic syndrome. Overall, disease-free and progression-free survival was 27%, 57%, and 25%, respectively.

Conclusion

Despite the treatment-related mortality, HDS is feasible, with satisfactory response rates, even in patients with poor prognosis.

Background

The early stem cell reservoir can be impaired by a few cycles of chemotherapy, and this impairment might persist after normalization of peripheral cytopenias. We directly evaluated the damage caused to marrow progenitor cells by 3 currently used chemotherapy regimens for advanced Hodgkin lymphoma.

Patients and Methods

Bone marrow samples from 37 patients randomly treated according to either the ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine), COPPEBVCAD (cyclophosphamide/vincristine/procarbazine/prednisone/epirubicin/bleomycin/vinblastine/lomustine/melphalan/vindesine), or BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone)schedule were taken a few days before the start of chemotherapy and 30 days and 6 months after its completion. Samples were cryopreserved, thawed in a single session, and cultured for 5 weeks to detect long-term culture-initiating cells (LTC-IC).

Results

On the basis of the numbers of LTC-IC detected and of their relative variations, the ABVD regimen was associated with the least early reduction and the best late recovery of LTC-IC. COPPEBVCAD produced the greatest early damage, but recovery was nearly complete by 6 months. BEACOPP caused intermediate early toxicity that persisted at 6 months.

Conclusion

The different late toxicity exerted on marrow progenitors by these chemotherapy regimens should be carefully weighed in relation to both the expected early response rate and subsequent possibility of rescue in the case of first treatment failure.

Four patients with a rapid clearance of leukemic cells maintained a molecular response after discontinuation of therapy. We adopted a new, more sensitive technique to detect minimal residual disease that can help to detect those patients who might be the most eligible for discontinuation when they achieve a complete molecular response.

Full Abstract

Only a restricted group of patients with Philadelphia chromosome—positive (Ph⁺) CML is able to achieve a complete molecular response (CMR) after treatment with imatinib. Clinical studies evaluating patients who discontinued treatment are ongoing, and initial reports have pointed out that approximately 50% of patients relapsed within 6 months. We report 4 cases of patients who stopped imatinib in sustained CMR, defined as BCR-ABL/ABL levels below a detection threshold of 5-log reduction and undetectable BCR-ABL transcript by qualitative polymerase chain reaction (PCR), either on BM and PB samples, in at least 2 samples. Cessation was due to some degree of toxicity. CCyR was reached within 3 months of imatinib therapy, and CMR was achieved after 12, 6 (2 cases), and 9 months. The duration of treatment before discontinuation was 43, 54, 16, and 51 months, respectively, while the median time of PCR negativity on imatinib was 36 months. Three patients did not relapse and are PCR-negative with a follow-up of 62, 47, and 41 months, respectively. The fourth patient stayed off of treatment in confirmed CMR for 28 months, until an RQ-PCR analysis on PB disclosed a BCR-ABL/ABL ratio of 0.0208%. She refused to restart imatinib, and she is currently off therapy after 1 year with an RQ-PCR still in the MMR range. Minimal residual disease was assessed with a new strategy with multiple PCR reactions on a 82-well plate, increasing the sensitivity to a 6-log reduction. Patients who remained persistently negative at standard PCR techniques behaved like the normal controls. The single patient who relapsed proved to be positive also in samples obtained during the PCR negativity at the standard methods. This report confirms that a molecular response can be sustained after discontinuation of imatinib. All patients were characterized by a rapid clearance of leukemic cells, suggesting that the kinetics of molecular response might predict prolonged remission after imatinib discontinuation. Furthermore, though in the literature all relapses occurred early, we observed a late molecular recurrence, not associated with progression. Finally we adopted a new, more sensitive technique to detect minimal residual disease that can help to detect those patients who can be the most eligible for discontinuation when they achieve a CMR.

Protein kinase C beta II expression in diffuse large B-cell lymphoma has prognostic significance not only for CHOP therapy in low-risk International Prognostic Index disease but also for all patients receiving CHOP plus rituximab.

Full Abstract

Introduction

Protein kinase C beta II (PKCbII) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy.

Aim

To compare the prognostic significance of immunohistochemically determined PKCbII expression in de novo DLBCL treated with CHOP chemotherapy (cyclophosphamide/doxorubicin/vincristine/prednisone) with and without rituximab.

Patients and Methods

80 consecutive patients treated at St. Vincent's Hospital with de novo DLBCL, 48 treated with CHOP, and 32 with R-CHOP (rituximab plus CHOP), were studied using immunohistochemistry for PKCbII on diagnostic tissue samples. Staining results were correlated with patient characteristics and clinical outcome. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method, and comparisons were determined by the log-rank test.

Results

PKCbII expression correlated with inferior OS and PFS in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0–2 adverse factors) but not in the overall patient group unstratified by IPI. PKCbII expression significantly correlated with inferior OS and PFS in R-CHOP—treated patients unstratified by IPI status.

Conclusion

PKCbII expression has prognostic significance not only for CHOP therapy in low-risk IPI disease but also for all patients receiving R-CHOP. Immunohistochemically demonstrated PKCbII expression thus identified patient subgroups in which alternative treatment strategies might confer superior outcome.

Imatinib is currently regarded as the best initial treatment for patients with chronic myeloid leukemia (CML). However, a significant proportion of patients who relapse, fail to respond, or develop intolerance might benefit from the use of second-generation tyrosine kinase inhibitors. In this review, we report the 2-year results in 8 clinical trials involving more than 2000 patients treated with dasatinib (phases I-III). Patients with CML who had failed to respond or were intolerant to imatinib were enrolled in a phase I trial. The positive results emanating from this study led to a series of 5 phase II trials known as START (SRC/ABL tyrosine kinase inhibition activity: research trials of dasatinib). In addition, 2 phase III dose-optimization trials have now been completed. These trials demonstrate that dasatinib offers clinical benefit to patients resistant or intolerant to imatinib, with a well-described and manageable adverse event profile.

We assessed the impact of selected apoptotic markers and adhesion molecules on the treatment outcome. Thirty newly diagnosed patients and 10 healthy subjects were studied. Proapoptotic markers (BCL2, p53, and CD95) and adhesion molecules (CD18, CD54) were assessed by flow cytometry before and after treatment. p21 mRNA was assessed by RT-PCR. Induction was done with the CVP regimen.

Full Abstract

The study included 23 men and 7 women. Median age was 66 years (range, 53-79 years). There were increases of p53 and BCL2 and reductions of CD18 and CD54 in cases compared to control. CD95 did not show significant increase compared to control. There were reductions in BCL2 after (versus before) treatment and increases in CD18 and CD54 after (versus before) treatment. Evaluable patients showed 11 complete remission (CRs; 39.3%), 7 (25%) partial remissions, 6 progressive diseases (21.4%), and 4 stable diseases (14.3%). The observation after treatment was 2 to 13 months. Median time to disease progression (TTP) of the responding patients was 9 months. Death was reported in 1 case. There was an increase in p53 and BCL2 expression in patients who did not achieve CR compared to those with CR and an increase in CD18 level in CR more than no-CR cases. No significant differences were found regarding the expression of CD95 and CD54 between both groups. Comparing the level of expression of the studied markers at initial presentation, there were increases in p53 and decreases in CD18 level in patients with no CR compared to those with CR. There was positive correlation between the expression of p53 and BCL2 and negative correlation between the p53 and CD18 and between BCL2 and CD18. There was significant negative correlation between TTP and BCL2 levels after treatment. Selected cases for p21 mRNA assessment showed negative correlation between p21 mRNA and p53 levels before treatment and decrease in p21 level was associated with poor prognosis and bad response to treatment. In conclusion, measurement of p53 and CD18 level can define a group of patients with aggressive disease who may require more aggressive therapy. BCL2 level after treatment is correlated with TTP.

Acknowledgment

The study was conducted at NCI-Cairo between 2004 and 2007.