Staging of mycosis fungoides/Sézary syndrome (MF/SS), the most common cutaneous T cell lymphoma (CTCL), is primarily based on the type and extent of skin involvement and the presence or absence of ...extracutaneous disease. In patients with large cell transformation, tumors, erythroderma, or abnormal lymph nodes on physical exam, staging includes CT scan to look for visceral or lymph node (LN) disease followed by biopsy of enlarged LN. Integrated PET/CT combines anatomic data from CT with functional data from PET and has been useful in the staging of many non-Hodgkin's lymphomas. To date, however, its role in staging MF/SS has not been investigated. We assessed the utility of integrated PET/CT in staging thirteen patients with MF (T2=1,T3=4,T4=1) or SS (T4B2=7) at high-risk for LN disease. Based on anatomic data from the CT component alone, only five of thirteen had enlarged LN (axillary/inguinal LN short axis ≥1.5cm or cervical LN short axis ≥1.0cm) and would have been referred for biopsy. In comparison, PET showed that all thirteen patients had hypermetabolic activity in at least one LN region. All patients had excisional LN biopsy and the extent of LN involvement was classified according to NCI criteria (LN1-4 classification). Six patients had LN1-3 and seven had effacement of LN architecture by lymphoma cells (LN4). Of the seven LN4 patients, four had SS and three had tumor MF. PET/CT helped identify the most suspicious LN region for biopsy, which led to the accurate stage of IVA. Notably, two patients had LN smaller than the CT size criteria and would have been incorrectly staged without the use of integrated PET/CT. Furthermore, we quantified the intensity of PET activity using standardized uptake value (SUV) and correlated this with LN grade. Patients with LN1-3 had a mean SUV of 2.7, median 2.2 (2.0–4.7) and patients with LN4 had a mean SUV of 5.4, median 3.9 (2.1– 11.8); p value 0.08. Ongoing analysis of additional patients may further define whether PET/CT can be used to significantly differentiate between LN1-3 vs LN4. Thus, for staging MF/SS, integrated PET/CT was more sensitive and specific in detecting malignant LN compared to CT alone and consequently provided more accurate staging and prognostic information. A larger scale study would be essential to confirm the superior staging capability of PET/CT over CT alone in MF/SS.
Summary of PET/CT correlation with LN pathology results in MF/SS
PatientT classMax SUVLN size (SA,cm)LN regionNCI gradeWHO gradeFinal stage1T32.01.2AxillaryLN11IIB2T42.11.3AxillaryLN11IIIB3T22.21.0InguinalLN21IIA4T44.71.0AxillaryLN21IIIB5T43.01.2InguinalLN21IIIB6T42.01.1InguinalLN32IIIB7T33.71.4CervicalLN43IVA8T43.21.5InguinalLN43IVA9T33.91.3InguinalLN43IVA10T411.83.2InguinalLN43IVA11T46.61.3InguinalLN43IVA12T46.32.1InguinalLN43IVA13T32.12.1AxillaryLN43IVAAbbreviations: T, tumor; SUV, standardized uptake value; LN, lymph node; SA, short axis; cm, centimeter
Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy. A resting LVEF of 50% is usually used as the lower limit of ...normal values. The decision to change chemotherapy, however, is complex and is affected by many factors, including ejection fraction.
To determine how LVEF data were used by clinical oncologists in clinical decision making, we performed a retrospective analysis of patients referred for ejection fraction measurements from the hematology/oncology divisionS of Stanford University from March 1992 through March 1995. The records of 565 patients treated with potentially cardiotoxic chemotherapy were evaluated.
LVEFs < 50% were found in 153 patients. The charts of patients with reduced ejection fractions were reviewed to determine if the radionuclide measurement resulted in either discontinuation of the cardiotoxic agent or substitution of a less cardiotoxic drug or mode of administration. These specific changes in therapy occurred in only 43 of the 153 (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection fractions < or = 40%. Patients with lower ejection fraction values were more likely to have their therapy changed than those with LVEFs close to normal. Patients with ejection fractions < or = 30 generally had cardiotoxic agents discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not changed, 81% had a normal increase in LVEF with exercise.
In clinical practice at our institution, ejection fraction < 50% is not used as an absolute contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%, potentially cardiotoxic therapy is most often discontinued or omitted. Radionuclide evidence of cardiac reserve may account for decisions to continue cardiotoxic agents despite ejection fractions < 50% in the majority of patients. Further study will be needed to establish standard criteria. Reserve function, as measured by the change in ejection fraction from rest to stress may be an important parameter used by oncologists to help select patients for continued therapy in spite of a reduced ejection fraction. Our results argue that use of fixed criteria may be too restrictive.
A potential mechanism of chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts ...from refractory or relapsed AML. In a multicenter phase II clinical trial, 37 patients with these poor risk forms of AML were treated with PSC 833 (Valspodar; Novartis Pharmaceutical Corporation, East Hanover, NJ), a potent inhibitor of the MDR-1 efflux pump, plus mitoxantrone, etoposide, and cytarabine (PSC-MEC). Pharmacokinetic (PK) interactions of etoposide and mitoxantrone with PSC were anticipated, measured in comparison with historical controls without PSC, and showed a 57% decrease in etoposide clearance (P = .001) and a 1.8-fold longer beta half-life for mitoxantrone in plasma (P < .05). The doses of mitoxantrone and etoposide were substantially reduced to compensate for these interactions and clinical toxicity and in Cohort II were well tolerated at dose levels of 4 mg/m2mitoxantrone, 40 mg/m2 etoposide, and 1 g/m2 C daily for 5 days. Overall, postchemotherapy marrow hypoplasia was achieved in 33 patients. Twelve patients (32%) achieved complete remission, four achieved partial remission, and 21 failed therapy. The PK observations correlated with enhanced toxicity. The probability of an infectious early death was 36% (4 of 11) in patients with high PK parameters for either drug versus 5% (1 of 20) in those with lower PK parameters (P = .04). P-gp function was assessed in 19 patients using rhodamine-123 efflux and its inhibition by PSC. The median percentage of blasts expressing P-gp was increased (49%) for leukemic cells with PSC-inhibitable rhodamine efflux compared with 17% in cases lacking PSC-inhibitable efflux (P = .004). PSC-MEC was relatively well tolerated in these patients with poor-risk AML, and had encouraging antileukemic effects. The Eastern Cooperative Oncology Group is currently testing this regimen versus standard MEC chemotherapy in a phase III trial, E2995, in a similar patient population.
Brentuximab vedotin is an antibody drug conjugate that induces durable objective responses in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. ...Fifteen of 160 patients who participated in two pivotal phase 2 studies received a consolidative allogeneic stem cell transplant (allo-SCT) following brentuximab vedotin treatment. This case series describes their experience. The studies were approved by Institutional Review Boards prior to patient enrollment. Patients received 1.8 mg/kg brentuximab vedotin every 3 weeks for up to 16 cycles. The estimated 2-year progression-free survival (PFS) rate was 66%, and the median PFS has not yet been reached. Eleven of the 15 patients were alive and the estimated 2-year survival rate was 80%. The safety of brentuximab vedotin treatment in this series was consistent with the known safety profile in this setting. Brentuximab vedotin is a compelling option for reducing tumor burden to facilitate a consolidative allo-SCT.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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