Treatment of RAEB-t with intensive chemotherapy and GM-CSF

A 55-yr old woman with refractory anaemia with excess of blasts in transformation developed prolonged bone marrow hypoplasia following two courses of mitozantrone and cytosine arabinoside. The administration of granulocyte-monocyte colony stimulating factor after two months of pancytopenia led to recovery of normal bone-marrow function, without any morphological evidence of myelodysplasia, which has persisted until the last blood count (6 months +).     

VMCP chemotherapy with or without interferon-alpha-2 in newly diagnosed patients with multiple myeloma

Fifty-two previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon (rIFN) alpha-2 and chemotherapy or chemotherapy alone. Patients were treated with vincristine, melphalan, cyclophosphamide and prednisolone every 4-6 weeks. In the combined treatment arm rIFN was administered concurrently with chemotherapy as well as during chemotherapy free intervals. The combined regimen effected 17/21 (80.9%) responses as compared to 19/27 (70.4%) responses in VMCP treated patients. Addition of rIFN to chemotherapy did not enhance hematologic toxicity. These findings suggest a somewhat higher rate of objective response in the VPMC + rIFN group, although a significant improvement in median survival by adding rIFN to conventional first line polychemotherapy in myeloma patients has not yet been achieved.     

Effect of all-trans-retinoic acid alone or in combination with chemotherapy in newly diagnosed acute promyelocytic leukaemia

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans-retinoic acid (ATRA) alone (45 mg m^-2) or with a simultaneous combination of ATRA (45 mg m^-2), daunorubicin (DNR, 50 mg/m^-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m^-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 10⁹/l at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 10⁹/l received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 10⁹/l) than in the group of patients receiving ATRA and chemotherapy (14.0 x 10⁹/l). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard ′3+7′ chemotherapy (DNR 45 mg m^-2,1 -3 days, ARA-C 200 mg m^-2,1-7 days) followed by two courses of standard ′2+5′ chemotherapy (DNR 50 mg m^-2 1-2 days, ARA-C 200 mg m^-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).     

Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma

BACKGROUND:

The addition of liposomal muramyl tripeptide phosphatidylethanolamine (MTP‐PE) to chemotherapy has been shown to improve overall survival in patients with nonmetastatic osteosarcoma (OS). The authors report the results of addition of liposomal MTP‐PE to chemotherapy for patients with metastatic OS.

METHODS:

Intergroup‐0133 was a prospective randomized phase 3 trial for the treatment of newly diagnosed patients with OS. The authors compared 3‐drug chemotherapy with cisplatin, doxorubicin, and high‐dose methotrexate (Regimen A) to the same 3 drugs with the addition of ifosfamide (Regimen B). The addition of liposomal MTP‐PE to chemotherapy was evaluated.

RESULTS:

Five‐year event‐free survival (EFS) for patients who received liposomal MTP‐PE (n = 46) was 42% versus 26% for those who did not (n = 45) (relative risk for liposomal MTP‐PE, 0.72; P = .23; 95% confidence interval [CI], 0.42‐1.2). The 5‐year overall survival for patients who received MTP‐PE versus no MTP‐PE was 53% and 40%, respectively (relative risk for liposomal MTP‐PE, 0.72; P = 0.27; 95% CI, 0.40‐1.3). The comparison of Regimen A with Regimen B did not suggest a difference for EFS (35% vs 34%, respectively; relative risk for Regimen B, 1.07; P = .79; 95% CI, 0.62‐1.8) or overall survival (52% vs 43%, respectively; relative risk for Regimen B, 1.1, P = .75; 95% CI, 0.61‐2.0).

CONCLUSIONS:

When the metastatic cohort was considered in isolation, the addition of liposomal MTP‐PE to chemotherapy did not achieve a statistically significant improvement in outcome. However, the pattern of outcome is similar to the pattern in nonmetastatic patients. Cancer 2009. © 2009 American Cancer Society.     

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.     

Treatment of newly diagnosed multiple myeloma

Multiple myeloma (MM) is the second most common oncohematologic disease. Most patients are older than 65 years at diagnosis, and different therapeutic options are available depending on the age of the patient. For those younger than 65 years, autologous stem cell transplantation is the standard of care, whereas in older patients the better choice is conventional chemotherapy. The introduction of thalidomide, bortezomib, and lenalidomide, which target MM cells and the bone marrow microenvironment, has changed the therapeutic options in newly diagnosed patients with MM.     

Choroid plexus carcinoma — responses to chemotherapy alone in newly diagnosed young children

Choroid plexus carcinoma (CPC) arising in the infant poses several treatment dilemmas. The tumor is often not totally resectable at presentation given its large size and tendency to invade adjacent brain. Because of its predisposition to regrow and metastasize, some form of postoperative cytotoxic therapy is required. Chemotherapy (CHT), as opposed to radiotherapy (RT), has 4 more desirable risk/benefit role in infants, since it is relatively sparing of late neurologic sequelae. Three young male children presented with large intraventricular CPC at 9, 18, and 27 months of age. One child had subarachnoid metastases at diagnosis and the other two had localized disease. Subtotal resections were accomplished and all three required VP shunts. Initial CHT consisted of four monthly courses of cisplatin (20 mg/m²) and etoposide (100 mg/m2), both administered intravenously, daily, for five days. After four courses, two children had complete responses and one had stable disease. Additional CHT was given but one child developed 4 local recurrence and another diffuse CNS metastases. Both died with intratumoral hemorrhages at 5 and 57 months following diagnosis. The third child remains in continuous remission 46 months after diagnosis. None of the children received RT. Chemotherapy may permit long term deferral of RT. More aggressive CHT regimens should be explored in infants with CPC.     

Preirradiation gemcitabine chemotherapy for newly diagnosed glioblastoma. A phase II study

BACKGROUND: The median survival for patients with glioblastoma is reported to be 12 months. To improve the outcome for glioblastoma patients, the authors evaluated the therapeutic efficacy of preirradiation gemcitabine chemotherapy followed by standard radiotherapy. METHODS: Twenty-one patients with newly diagnosed glioblastoma were enrolled in a prospective unicenter trial of preirradiation gemcitabine chemotherapy. Chemotherapy included up to 4 monthly cycles of intravenous gemcitabine (Day 1, Day 8, and Day 15; 1000 mg/m2). Involved field radiotherapy was given after chemotherapy or earlier in the case of disease progression or gemcitabine intolerance. RESULTS: With gemcitabine chemotherapy alone, there was a median progression free survival of 11 weeks and a progression free survival rate at 4 months of 24%. In 18 of 21 patients who subsequently received a full course of radiotherapy, the median progression free survival from the time of diagnosis was 8 months and the progression free survival rate at 12 months was 17% (3 of 18 patients). The median overall survival was 11 months. There was no specific treatment-related neurotoxicity reported. Neither age nor extent of residual postoperative tumor predicted the duration of progression free survival in patients treated with gemcitabine chemotherapy alone or in those treated with gemcitabine plus radiotherapy. CONCLUSIONS: Gemcitabine followed by radiotherapy is a safe regimen for patients with newly diagnosed glioblastoma but the gemcitabine schedule used in the current study did not appear to confer any survival advantage compared with standard involved field radiotherapy alone.     

A pilot study of EVAP/ABV chemotherapy in 25 newly diagnosed children with Hodgkin's disease.

Twenty five children with newly diagnosed Hodgkin''s disease were clinically staged and treated with a chemotherapy protocol designed to reduce delayed toxicity. Four patients without macroscopic residual disease after biopsy received three cycles of hybrid EVAP/ABV. All remain in CR 31-46 months from diagnosis. One other developed fever and rash considered to be due to Ara-C and was treated with MOPP. Twenty patients had macroscopic residual disease after biopsy and were treated with two cycles of EVAP alone and reassessed with imaging and gallium scans. Twelve achieved CR, seven PR and one was not evaluable. Patients in CR were subsequently treated with 2-4 cycles of hybrid EVAP/ABV, while those in PR received 3-4 cycles. At a median follow up of 37 months the overall survival was 100%, relapse free 79% and treatment failure free 60%. Eight patients had mediastinal widening > 1/3 thoracic width. At the completion of the protocol five achieved CR, two PR and one was withdrawn from study at investigator preference. One patient has subsequently relapsed. Of the evaluable ten patients without a mediastinal presentation all achieved CR but three relapsed at 10, 13 and 18 months from diagnosis. Patients who achieved a PR only, relapsed or were withdrawn from study have been salvaged with MOPP or Ch1VPP chemotherapy.     

Timed-sequential chemotherapy with concomitant granulocyte colony-stimulating factor for newly diagnosed de novo acute myelogenous leukemia.

EMA, consisting of etoposide, mitoxantrone, and cytarabine, is a timed-sequential chemotherapy (TSC) regimen and an efficacious option for induction treatment of acute myelogenous leukemia (AML). Hematopoietic growth factors (HGFs) have been shown to recruit leukemic blasts into cell cycle. We postulated the addition of granulocyte colony-stimulating factor (G-CSF) to EMA (EMA-G) might enhance treatment efficacy. EMA-G consisted of mitoxantrone on days 1-3, cytarabine on days 1-3 and 8-10, etoposide on days 8-10, and G-CSF from day 4 until absolute neutrophil count (ANC) >500/microl. In total, 28 patients were enrolled. All patients had newly diagnosed de novo AML. The median age was 42 years. Of the 27 patients with cytogenetic analysis, six had favorable karyotype, 18 intermediate karyotype, and three unfavorable karyotype. The median follow-up was 37.5 months. The median time for both ANC recovery and last platelet transfusion was 26 days. The toxicities associated with this regimen were no more than those expected with the standard chemotherapy. In all, 24 (86%) patients achieved complete remission (CR), three (11%) patients had no response, and one patient died within 24 h of induction therapy before response could be evaluated. Of the 24 patients who achieved CR, 22 received high-dose cytosine arabinoside and two received allogeneic bone marrow transplant as initial postremission therapy. For the whole cohort, the estimated 3-year survival rate was 67%. The median relapse-free survival was 30.5 months. We conclude that EMA-G regimen is a safe regimen and administration of G-CSF during and after induction treatment is not associated with prolongation of marrow aplasia or acceleration of leukemia relapse. It is efficacious for induction therapy for newly diagnosed de novo AML. A high CR rate can be achieved with only one course of this chemotherapy.     

Phase II study of propranolol feasibility with neoadjuvant chemotherapy in patients with newly diagnosed breast cancer

Purpose

To determine the nature and severity of vasomotor symptoms, sexual problems, mood and sleep disturbance in community-dwelling breast cancer patients, whether and where they received treatment for these symptoms and their satisfaction with treatment received.

Methods

Online cross-sectional survey distributed through Breast Cancer Network Australia (BCNA).

Results

524/2286 women responded to the invitation to participate. Of these, 74% (385/523) reported symptoms of interest and were included in the analysis. Mean age was 55.2 years and mean time since breast cancer diagnosis was 5.7 years. Most (66%) had received chemotherapy and were taking endocrine therapy (64%). The most common symptoms were hot flushes/night sweats and sleep disturbance (both 89%), vaginal dryness (75%), mood swings (62%) and sexual problems (60%). Symptoms were mild (21–33%) or moderate (21–38%) in around one third and severe in up to one quarter (8–26%). Symptoms affected the ability to “get on with their life” for 36%, predicted by severity of hot flushes (OR 1.4), sleep disturbance (OR 1.3), mood disturbance (OR 1.3), and sexual problems (OR 1.3). Only 32% were offered treatment, mostly delivered by GPs (33%) or oncologists (26%). Only 49% found this “somewhat effective” and 34% found it ineffective. The majority (60%) wanted more support to manage their symptoms.

Conclusion

Menopausal symptoms, sexual problems, mood and sleep difficulties are common after breast cancer and often not effectively managed. There is an unmet need for coordinated care providing effective treatments.

     

硼替佐米为主方案治疗初发多发性骨髓瘤临床研究

目的观察以硼替佐米为主方案治疗初发多发性骨髓瘤的临床疗效及不良反应。方法回顾性分析本院15例以硼替佐米为主方案治疗初发多发性骨髓瘤的临床资料,疗效评定采用中国多发性骨髓瘤诊治指南标准,不良反应标准参照美国国立癌症研究所的常规毒性判定标准3.0版NCI-CTCAE。结果 15例中位随访16月,完全缓解/接近完全缓解(CR/nCR)8例,非常好的部分缓解(VGPR)2例,部分缓解(PR)2例,微小缓解(MR)1例,无变化(NC)1例,疾病进展(PD)1例,有效率80.0%(12/15)。15例患者中主要不良反应有胃肠道症状(60.0%)、周围神经病变(66.7%)、白细胞减少(46.7%)、血小板减少(55.6%)、感染(23.3%),少见不良反应有心律失常、心功能不全。结论硼替佐米为多发性骨髓瘤患者的治疗提供了有效的途径,该药起效快,缓解率高,安全性好。     

Antifungal prophylaxis in newly diagnosed AML patients–Adherence to guidelines and feasibility in a real life setting

Antifungal posaconazole prophylaxis for AML patients receiving induction chemotherapy has been routine at our centre since 2009. This retrospective study examined the feasibility and practicability of our prophylaxis guidelines in clinical practice. Data sets of 90 patients undergoing induction‐chemotherapy for AML between 2011 and 2014 were evaluated regarding adherence to local guidelines for the administration of antifungal prophylaxis with posaconazole. 75.5% of the 90 patients received posaconazole prophylaxis. All but eight patients received the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan measured twice weekly. Contradicting our guidelines, 89.70% of patients received concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis discontinued and started empirical antifungal treatment in the absence of diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven, probable and possible) with 7.35% of infections being classified as proven or probable. Although limited by a small sample size, our study demonstrates the feasibility of local guidelines in a real life setting and outlines areas for improvement in both guidelines and clinical practice. We also highlight the importance of ensuring awareness of guidelines and raise questions about a uniform approach to antifungal prophylaxis in AML patients.     

酞咪哌啶酮联合化疗初治多发性骨髓瘤疗效观察

目的:探讨酞咪哌啶酮(thalidomide,商品名反应停)联合化疗初治多发性骨髓瘤(multiplemyeloma,MM)的初步疗效。方法:治疗组14例初治多发性骨髓瘤应用反应停起始剂量100mg/d~200mg/d,每2周增加100mg~200mg直到患者能够耐受,最大剂量不超过600mg/d,同时联合以马法兰为主的MP或M2方案化疗;对照组20例初治多发性骨髓瘤单用MP或M2方案化疗。观察比较两组的3个月有效率、1年无事件生存率(EFS)和2年总生存率(OS)。结果:有效(部分缓解加进步)率治疗组为85.7%,对照组为50%。1年EFS治疗组为71.4%,对照组为35%。2年OS治疗组为57.1%,对照组为25%。反应停治疗组副作用可以耐受,便秘最常见。结论:反应停联合化疗可提高初治MM的疗效和1年EFS、2年OS。     

Increased whole-body protein turnover in sick children with newly diagnosed leukemia or lymphoma

Using a single dose, [15N]glycine turnover technique, whole body rates of proteins synthesis and breakdown were assessed in six healthy children and in eight children with newly diagnosed leukemia (DeWys, W. D. Cancer Res., 42: 721s-726s, 1982) or lymphoma (Baracos, V., Rodemann, H. P., Dinarello, C. A., and Goldberg, A. L. N. Engl. J. Med., 308: 553-558, 1983). Based on excretion of 15N as urinary ammonia, synthesis (g protein per kg body weight per day) was significantly (p less than 0.025) higher in the cancer patients [5.4 +/- 1.5 (S.D.)] compared to the controls (3.6 +/- 0.9); breakdown was also higher (p less than 0.02) in the patients (5.5 +/- 1.8) compared to the controls (3.1 +/- 1.1). When only the seven patients with leukemia were considered, there also were significant increases in synthesis (5.4 +/- 1.6, p less than 0.05) and breakdown (5.4 +/- 1.9, p less than 0.025) compared to controls. Increases in both synthesis and breakdown were also observed in the patients when the protein turnover data were expressed as a function of the rate of creatinine excretion or the calculated lean body mass. We conclude that whole body protein turnover is increased in sick children at the time of diagnosis with some forms of newly diagnosed cancer.     

CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P =. 095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.