Cycles Of Combination Chemotherapy Research Articles

Tetra-Arsenic Tetra-Sulfide Containing Triple-Agent Regimen as the First Line Therapy for Acute Promyelocytic Leukemia: Expeditiously Consecutive Complete Remission and Improved Disease-Free Survival.

Our previous study has demonstrated that tetra-arsenic tetra-sulfide (As4S4) treatment alone is highly effective and safe in both induction and maintenance therapy in acute promyelocytic leukemia (APL) patients (Lu DP et al, Blood 2002; 99: 3136). In current clinical study, we explored whether As4S4 combined sequentially or simultaneously with all-trans retinoid acid (ATRA) and cytotoxic agents according to specific clinical condition as the first line therapy could expedite complete remission (CR) but in a safer way and further improve disease-free survival (DFS). The treatment-related toxicities were also studied. From April 2001 to May 2007, 114 patients with APL in a median age of 32.5 years (10–73 years) were enrolled including consecutive 68 newly diagnosed cases and 46 patients in hematological remission. For induction therapy, both As4S4 (60 mg/kg) and, if leukocytosis or retinoid acid syndrome was not a risk, ATRA (25mg/m2) were taken orally per day till CR. Cytotoxic agents such as mitoxantrone and/or hydroxyurea were added when WBC counts were more than 4 × 109/L. After hematological remission, 4 to 6 cycles of combined chemotherapy were given, and followed by alternatively oral use of As4S4 (3 cycles) and ATRA (1 cycle) in outpatient base for maintenance therapy until 4 years after diagnosis. PML/RARa transcript was monitored quantitatively by real-time PCR. Arsenic levels in blood and urine were also monitored with an atomic absorption spectrophotometer. Consecutive 68 newly diagnosed patients all achieved complete hematological remission in a median time of 29.5 days (14 – 62 days) without early death. The median time to achieve molecular remission was 61.5 days (34 – 120 days). Four out of 114 patients relapsed. One of them had obtained CR again. One patient died from leukemia relapse. Treatment with As4S4containing regimen was well tolerated. Mild gastrointestinal discomfort, transient elevation in liver enzyme, rash, and edema were noted in a few cases. Estimated DFS rate for 4 years was 94%, with a median follow-up time of 36.5 months (3–76 months). Our encouraging results show that faster consecutive CR, higher DFS rate and better quality of life have been achieved with the above regimen as the first line therapy for APL patients.

Current treatment options in uterine endometrial stromal sarcoma: report of a case and review of the literature

Uterine sarcomas are a rare form of uterine cancer. They occur in women from 40 to 60 years and are generally characterized by poor prognosis, a high rate of local recurrence, and distant metastases. Endometrial stromal sarcoma (ESS) accounts for 0.2% of all gynecological malignancies. Forms of possible treatment include surgery, radiotherapy, chemotherapy, and endocrine treatment. Randomized trials analyzing these treatment options are limited due to the rarity of this disease; therefore, a standard therapy could not be established thus far. To present an overview of the current treatment options of ESS, a search of Medline, Embase, and the Cochrane Library was performed and the results concluded. We report the case of a 32-year-old woman who presented with FIGO stage II ESS. Initial treatment with tamoxifen and local perfusion with cisplatin resulted in disease progression and were discontinued. A novel, therapeutic approach using two cycles of combination chemotherapy with doxorubicin and ifosfamide followed by surgery was applied. Five years after surgery, the patient is still in complete remission. Thus, we conclude that although there is no data from randomized trials available, chemotherapy in advanced or metastatic ESS can provide an opportunity for surgical treatment and can lead to long-term remission.

Phase I/II Study of CPT-11 plus UFT in Patients with Advanced/Recurrent Colorectal Cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG): Protocol 0102

The primary objective of this study was to explore the efficacy and safety of combined chemotherapy with CPT-11 and UFT in patients with advanced/metastatic colorectal cancer. Twenty-two patients with metastatic colorectal cancer were enrolled in the phase I trial and 35 patients (including eight patients treated at level 4 during phase I) were evaluated in the phase II trial. Treatment consisted of two 35-day cycles of combination chemotherapy with CPT-11 and UFT. During phase I, CPT-11 was administered on days 1 and 15 as an intravenous infusion over 90 min at four different dose levels, starting from a dose of 80 mg/m2 (level 1). During phase II, the dose of CPT-11 was fixed at 150 mg/m2 based on the results of the phase I study. UFT was administered orally at a fixed dose of 300 mg/m2 on days 1-28, followed by a 1-week drug holiday, during each course (35 days). The maximum tolerated dose (MTD) of CPT-11 was determined to be 150 mg/m2 during the phase I trial. The major toxicities detected during phase II in 35 patients receiving CPT-11 at this recommended dose were grade 3/4 neutropenia in nine patients (25.7%) and grade 3/4 anorexia in six patients (11.4%). No severe adverse events occurred. The overall response rate and the median overall survival time was 22.9% (8/35) and 23.9 months for all patients, respectively. For pre-treated patients they were 26.3% (5/19) and 25.1 months, respectively. This combination of CPT-11 and UFT is considered to be both feasible and relatively safe. The response rate of the patients receiving CPT-11 at a dose of 150 mg/m2 was comparable to that reported previously for 5-FU-based regimens coupled with CPT-11, and this regimen can probably be beneficial for patients with pre-treated advanced colorectal cancer on an outpatient basis.

Endodermal sinus tumor diagnosed in pregnancy: a case report

Pure endodermal sinus tumor (EST) of the ovary is an uncommon germ cell tumor characterized by rapid growth. Its occurrence during pregnancy is extremely rare. The case of a 34-year-old woman with EST stage IC diagnosed in the 22nd week of gestation is presented. She received four cycles of cisplatin monotherapy during pregnancy. Further, three cycles of combination chemotherapy (cisplatin, bleomycin, and etoposide) were administered. Twenty-eight months posttreatment the patient was in complete remission with good health. A healthy female infant was delivered by cesarean section in the 35th week of pregnancy. The child showed normal laboratory, pediatric, and neurologic examination at the time of discharge from hospital and during the first and second years of her life. We conclude that the prognosis of EST is very good if patient receives adjuvant therapy. Cisplatin monotherapy seems to be effective and safe during pregnancy.

Incidence and risk factors of central nervous system recurrence in aggressive lymphoma—a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)

Central nervous system (CNS) relapse is a devastating and usually fatal complication of aggressive lymphoma. The extent of the disease, the proliferation rate and the sites of extranodal involvement have been discussed as risk factors. We analyzed the patients treated on protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL) between 1990 and 2000, evaluated the rate and prognostic factors for CNS recurrence and developed a risk model trying to identify subsets of patients suitable for future prophylactic strategies. From 1993 to 2000, 1399 patients [<or=60 years with normal lactate dehydrogenase (LDH) and >60 years irrespective of LDH] were randomized to receive six cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-21, CHOP-14 or six cycles of CHOP+etoposide (CHOEP)-21, CHOEP-14 in a 2x2 factorial study design in the NHL-B1/B2 studies. From 1990 to 1997, 312 patients<or=60 years with an elevated LDH were randomized to five cycles CHOEP+involved field (IF) radiotherapy or three cycles CHOEP followed by high-dose BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem-cell transplantation (NHL-A study). A total number of 1711 patients were initially eligible for this study, of whom 18 patients had to be excluded due to primary CNS involvement. In the remaining 1693 assessable patients, 37 cases of relapse or progression to the CNS (2.2%) were observed. The protocol asked for an intrathecal (i.th.) prophylaxis in patients with lymphoblastic lymphoma only (n=17), but overall 71 patients (71 of 1693=4.2%) received prophylaxis by decision of the treating physicians. Multivariate Cox regression analysis identified increased LDH (P<0.001) and involvement of more than one extranodal site (P=0.002) as independent predictors of CNS recurrence in the NHL-B1/B2 study population. Treatment with etoposide also evolved as a prognostic factor because the risk of CNS failure was significantly reduced after CHOEP (P=0.017). Elderly patients presenting with both an elevated LDH and lymphoma involvement in liver, bladder or adrenals had an up to 15-fold risk of spread of the disease to the CNS. The incidence of CNS relapse in 1693 patients treated for aggressive lymphomas on DSHNHL protocols from 1990 to 2000 was low (2.2%), although CNS prophylaxis was administered to <5% of patients. Thus, a general prophylaxis for all patients is not warranted, the less so since the effectiveness of i.th. prophylaxis itself is judged controversially. Increased LDH and involvement of more than one extranodal site were confirmed as independent risk factors. A cumulative 20% incidence of CNS disease in certain prognostic subgroups of elderly patients may render these candidates for i.th. prophylaxis; however, this approach would imply a potential overtreatment of approximately 80% of these patients deemed at high risk.

Post-irradiation angiosarcoma of bone

Radiation therapy is extensively used for treatment of malignancies, but angiosarcomas occurring in an irradiated area are uncommon. We report a rare case of high-grade epithelioid angiosarcoma of upper end of right humerus in a 67-year-old male occurring ten years following irradiation for giant cell tumor of the same anatomical site. The patient presented with progressive painful swelling over right shoulder and his X-ray showed erosion of medial cortex with lytic areas at upper end of humerus. He underwent excision of affected part of humerus followed by cemented hemiarthroplasty and bone grafting. After initial histopathological diagnostic dilemma the final report was given as post-radiation angiosarcoma. Disease recurred at the end of one-year follow-up period where upon he underwent wide resection with prosthesis replacement. He received four cycles of combination chemotherapy with doxorubicin and ifosfamide and currently is free of recurrence after six months follow-up.

Mixed or metachronous germ-cell tumor?

We report the extremely rare occurrence of a second germ-cell tumor at a different site and with different histological types long after total resolution of a pineal germinoma. A 21-year-old man who presented with headache and diplopia was admitted to our hospital. Neuroradiological studies revealed a tumor in the pineal region. The tumor was biopsied with endoscope, and third ventriculostomy was performed. Histologically, the tumor proved to be a germinoma. The patient received 3 cycles of combination chemotherapy consisting of carboplatin and etoposide with radiotherapy. The tumor was totally resolute. Twelve months later, he was readmitted with headache and diplopia. Neuroradiological studies showed a tumor in the right temporal lobe. The second tumor was totally removed. Histologically, the tumor proved to be a mixed germ-cell tumor, which consisted a yolk-sac tumor and a germinoma. After the second course of chemotherapy, magnetic resonance image studies revealed no evidence of the tumor. The second tumor was considered to be a metachronous neoplasm rather than a recurrence of the original mixed germ-cell tumor, which consisted a yolk-sac tumor and a germinoma.

Resultados a largo plazo del tratamiento con quimioterapia y radioterapia en linfoma no Hodgking localizado, de grados intermedio y alto

Treatment of intermediate and high grade non-Hodgkin lymphoma (NHL) includes chemotherapy with or without radiotherapy, depending on the clinical stage. The standard treatment for advanced NHL is 8 cycles of combined chemotherapy, cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Patients presenting with localized disease are treated with fewer chemotherapy cycles and involved field radiotherapy, with good results. To evaluate the treatment results including overall survival (OS) and event-free survival (EFS) in localized aggressive NHL patients treated at the Pontificia Universidad Católica de Chile, Clinical Hospital. Retrospective analysis of all patients with Ann Arbor stages I and II referred to the hematology and radiotherapy clinic between 1998 and 2003. OS and EFS analysis was made according to the Kaplan and Meier method. Log-rank and Cox methods were used for univariate and multivariate analyses, respectively. Chemotherapy and radiotherapy toxicities were scored according to World Health Organization (WHO) and Radiation Therapy Oncology Group (RTOG) scales, respectively. 39 patients (20 men), aged between 20 to 85 years, were the source for this study. The average follow-up was 51 months (range 6-115). The 5 years OS and EFS were 72,4% and 63,3%, respectively. On univariate analysis, age over 60 was the only variable that affected negatively OS and EFS. Acute toxicity caused by chemotherapy and radiotherapy was uncommon. Age over 60 was the only independent variable associated with poor prognosis. The number of chemotherapy cycles and the drug combination did not influence the results. These results support the usefulness of a shortened chemotherapy regimen plus involved field radiotherapy.

Syringoid eccrine carcinoma with apparently aggressive transformation: case report and review of the literature

A 65-year-old man presented with a 20-year history of a lesion on his lower abdomen. The lesion had started as an indolent papule that slowly developed to form an extensive plaque. Physical examination revealed a flat-topped, elevated, well-demarcated, erythematous plaque measuring 7 cm × 5 cm in diameter (Fig. 1). The lesion had an elastic, hard induration beneath the plaque and was fixed to the underlying tissue. Inguinal lymphadenopathy was present. Hematologic and biochemical investigations were all within the normal ranges. The patient underwent incision biopsy. Figure 1. Clinical appearance of the lesion. An indurated plaque can be seen on the lower abdomen Download figure to PowerPoint A biopsy specimen, measuring 2.7 cm, revealed that the tumor was located in the dermis, and consisted of solid nests and small cords in a dense fibrocollagenous stroma. The tumor located in the upper dermis consisted mainly of solid nests with calcified central necrosis (Figs 2 and 3). The tumor located in the deep dermis consisted of small cords forming luminal, tubular, and tadpole-shaped structures, resembling those of syringoma (Figs 2 and 3). Solid tumor nests consisted of tumor cells which were basaloid and polymorphic, with hyperchromatic nuclei. A few mitotic figures were observed. A palisading arrangement of tumor cells was not observed at the periphery of the solid tumor nests. Keratinous cysts and follicular differentiation were not observed. No apocrine differentiation, such as decapitation secretion, was observed. There were no connections between the tumor nests and the epidermis. The extent of tumor invasion could not be determined from the biopsy specimen because the tumor had spread beyond the edges of the excision. Immunohistochemical analysis showed diffuse nuclear and cytoplasmic positivity for S-100 protein (1 : 1000; Dakopatts, Glostrup, Denmark) and focal positivity for carcinoembryonic antigen (CEA, 1 : 500; Mochida, Tokyo, Japan). Figure 2. The tumor consisted of solid undifferentiated nests and small cords forming tubular structures in a dense fibrocollagenous stroma (original magnification, ×40) Download figure to PowerPoint Figure 3. The tumor located in the upper dermis consisted mainly of solid undifferentiated nests with calcified central necrosis. Small cords forming tubular structures resembling those of syringoma can also be observed (original magnification, ×200) Download figure to PowerPoint The extent of tumor spread was evaluated by computed tomography (CT) and magnetic resonance imaging. The primary tumor had infiltrated the rectus abdominis muscle, and multiple metastases, up to 1 cm in diameter, were observed in the lungs, right bronchus, para-aortic lymph nodes and Th11, right S1, and bilateral ilium. CT scan revealed no continuity between the tumor and the prostate. After consulting a urologist, the possibility of prostate cancer was ruled out. After diagnosis and evaluation of tumor spread, the patient was treated with seven cycles of combination chemotherapy as follows: 5-fluorouracil (350 mg/m2 intravenously) on days 1–5, epirubicin (40 mg/m2 intravenously) on day 1, mitomycin C (3.5 mg/m2 intravenously) on day 1, vincristine sulfate (0.7 mg/m2 intravenously) and carboplatin (300 mg/m2 intravenously) on day 2, every 21–28 days. The treatment was relatively well tolerated without major complications. After seven courses of chemotherapy, evaluation by CT showed no change in the size of the primary lesion, or in the size and number of distant metastases. It is now 6 months since the last course of treatment and the patient appears to have stable disease.

Pure non‐gestational choriocarcinoma of the ovary diagnosed by DNA polymorphism analysis

Pure primary ovarian choriocarcinoma is a rare condition that can be of gestational or non-gestational origin. Non-gestational choriocarcinoma has been found to be resistant to single-agent chemotherapy and has a worse prognosis than gestational choriocarcinoma, but it is difficult to distinguish the two types by routine histological examination. Herein is reported a case of primary pure non-gestational choriocarcinoma of the ovary in a 33-year-old nulligravid woman, as confirmed by DNA polymorphism analysis. All tested microsatellite markers had identical DNA profiles with the same allelic sizes between the tumor and the myometrium of the patient, who was homozygous for three markers (BAT26, BAT25 and D17S250) and heterozygous for four (D2S123, D18S57, DCC and D18S58), supporting non-gestational origin. The patient has no evidence of disease 17 months after surgery and four cycles of combination chemotherapy. This case demonstrates the usefulness of DNA polymorphism analysis for the determination of the origin of extrauterine choriocarcinoma. Clinical relevance of this method needs to be further studied and substantiated.

Hemolytic uremic syndrome following the infusion of oxaliplatin: case report

BackgroundOxaliplatin is a platinum derivative, which is used in the treatment of colorectal cancer. A small number of oxaliplatin-related hemolytic and/or thrombocytopenic reactions have been reported. We present a case of hemolytic-uremic syndrome that developed during the 4th cycle of combination chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin.Case presentationA 52-year-old-male was administered chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin for a Duke's stage C colorectal carcinoma. Three cycles of chemotherapy had been administered without complications when, at the beginning of the fourth cycle, the patient developed clinical and laboratory abnormalities consistent with the development of the hemolytic-uremic syndrome. Treatment was discontinued; the patient was managed with monitored IV hydration and loop diuretics, high dose corticosteroids and fresh frozen plasma infusions and recovered completely.ConclusionThe hemolytic-uremic syndrome may be a rare complication of oxaliplatin-based chemotherapy. Clinicians need to maintain a high index of suspicion to diagnose and treat this life-threatening adverse event.

Sister Mary Joseph's Nodule as a Presenting Sign of Internal Malignancy

CASE 1: A 64-year-old, otherwise healthy woman was referred to the surgery clinic for a presumed umbilical hernia. On physical examination, a cutaneous nodule was noted on the umbilical region and the patient was referred to the dermatology clinic. The patient was reexamined and an erythematous nodule was observed in the umbilicus measuring 2.5 cm in diameter. The patient denied pain, change in bowel habits, or weight loss. There were no other abdominal masses, no sign of ascites, and no regional lymphadenopathy. A skin biopsy from the nodule showed mucinous adenocarcinoma. Immunohistochemical staining was positive for carcinoembryonic antigen, and negative for cytokeratin (CK)7 and CK20. These results were consistent with a Sister Mary Joseph's nodule and led to the diagnosis of an occult colon carcinoma. The patient had no risk factors for colorectal carcinoma. The patient underwent surgery in another hospital, and died 3 months after the initial diagnosis of Sister Mary Joseph's nodule. CASE 2: A 73-year-old woman was referred to the dermatology clinic for evaluation of a painful, ulcerated, 3-cm lesion in the umbilicus (Figure 1). She was otherwise asymptomatic. A skin biopsy showed neoplastic glandular cells infiltrating among collagen bundles (Figure 2). Stainings for mucin and for CK7 were positive, while staining for CK20 was negative. An abdominopelvic CT scan demonstrated a 3.5-cm space-occupying lesion in the liver. Results of gastroscopy, colonoscopy, chest computed tomographic (CT) scan, and mammography were normal. Serum levels of the tumor-associated protein CA125 were elevated to 164 units, while those of CA 19-9 and carcinoembryonic antigen were within normal range. A gynecologic examination and a transvaginal ultrasound were normal. The patient had no personal or family history of any malignancy or any risk factors for developing a carcinoma. The patient was scheduled for a palliative resection of the umbilical nodule, combined with a laparoscopic inspection in search of the undetected primary tumor. She refused surgery and was lost to follow-up. She died 4 months after the initial diagnosis of umbilical metastasis. CASE 3: A 51-year-old man was aware of a silent mass in his umbilicus for 2 years without seeking medical advice. Following 2 weeks of increasing pain in this area, he was referred to the emergency room for a suspected incarcerated umbilical hernia. Surgery revealed a mass attached to the fascia and peritoneal fat. The mass was removed and diagnosed as a poorly differentiated adenocarcinoma, staining positively for carcinoembryonic antigen, and negatively for CK20, CK7, prostate-specific antigen, and prostatic acid phosphatase. Both gastroscopy and colonoscopy failed to detect the primary tumor. An abdominopelvic CT scan was normal, but a CT scan of the chest disclosed a nodule measuring 2.5 x 1.5 cm in the lower lobe of the right lung. On bronchoscopy, it was found to be an invasive adenocarcinoma, consistent with a primary tumor of the lung. The patient was a heavy smoker (45 pack-years). The patient received 4 cycles of combined chemotherapy with carboplatine and gemcitabine, with no improvement. A month later, the patient complained of abdominal pain. Following demonstration of intra-abdominal spread of disease by CT scan, a second line chemotherapy was instituted with paclitaxel. A month later the patient's condition deteriorated and he complained of cough, sweating, and pain along the right leg. A bone scan revealed bone metastases in the right femur and left tibia. Two weeks later he was admitted to the hospital with intestinal obstruction and underwent laparotomy. He had massive intra-abdominal spread of cancer and ascites. Only a palliative colostomy was performed. The patient died 3 weeks later, 9 months after the diagnosis of adenocarcinoma of the lung. The clinical data on the three patients are summarized in Table I.

Neoadjuvant and adjuvant chemotherapy without radiation for esophageal cancer

4054 Background: A Phase II trial to evaluate neoadjuvant (NAD) and adjuvant (AD) combination chemotherapy (CT) without radiation therapy (RT), for Stage III esophageal adenocarcinoma. Methods: Stage III disease by CAT scan or EUS and ECOG performance status 0–1. The CT cycles included Cisplatin, Taxol, FUDR and Leucovorin. The chemotherapy was given for 16 weeks prior to surgery, followed by adjuvant chemotherapy for patients whose pathology at the time of surgery demonstrated microscopic disease. Survival was estimated via Kaplan Meier. Results: 33 patients were enrolled: 28 completed NAD, 15 received AD. Of 33 pts given NAD, 16 had grade I/II toxicity and 14 had grade III/IV. In addition, 6 of 15 pts receiving AD had grade I/II toxicity and 3 had grade III/IV during that phase of treatment. Thirty-two (32) patients went to surgery, 30 patients were resected: 24 transhiatial and 6 transthoracic. Of the 28 patients who completed NAD, 19 (68%) demonstrated improvement in dysphagia; 11 (41%) gained weight, and 7 (26%) had no weight change. Pathologic response to NAD: 30 patients had partial response and 2 patients had progressive disease, one died prior to surgery, post carotid endarterectomy. Ten (10) patients showed no gross disease. Twenty-three (23) patients have expired, 17 disease related with distant metastasis, 1 with local recurrence and distant metastasis, 3 non-disease related and 2 unresectable cases. Kaplan-Meier estimates of overall survival at 1, 3, and 5 years were 73% (95% CI: 58 to 88%), 52% (95%CI: 34 to 69%), and 29% (95% CI: 13 to 45%), respectively. Median survival was 42 months (95% CI: 14 to 52 months). Ten (10) patients are alive after a median follow up of 73 months (range 45 to 89). Seven (70%) of the surviving patients received both NAD (2 cycles) and AD (1 to 2 cycles) and all had no evidence of disease as of last clinical and radiological evaluation. Conclusions: This regimen of combination CT for locally advanced esophageal adenocarcinoma is safe and comparable with those regimens that contain RT. There has been 1 local recurrence; 17 patients have recurred distantly. Omission of RT may allow for a more aggressive CT and reduction in the local complications post-surgery. This study needs to be confirmed in a larger phase II or in randomized phase III trial. No significant financial relationships to disclose.

Non-Hodgkin's lymphoma in patients 80 years of age or older

BackgroundVery elderly patients (≥80 years old) with non-Hodgkin's lymphoma (NHL) frequently have co-morbid conditions and are generally excluded from clinical trials or even from treatment. The optimal treatment of these patients is unknown. Patients and methodsWe reviewed the records of 109 patients ≥80 years at diagnosis of NHL (65 F/44 M; median age: 84 years, range; 80–95). ResultsSeventy-eight patients (72%) had aggressive NHL, 25 (23%) had indolent and NHL, eight had unclassified disease. Advanced-stage disease was noted in 54%. Forty patients (39%) had a poor ECOG performance status (PS), and 52 (49%) had an intermediate or high risk International Prognostic Index (IPI). Seventy-nine patients (72%) were treated with chemotherapy and 37 (34%) with radiotherapy. Initial chemotherapy consisted of chlorambucil in 15, oral etoposide in 2, and combination protocol in 62. Only 16% of patients received full-dose therapy, and only 50% completed ≥6 cycles of combination chemotherapy. The overall response rate for the 69 evaluable patients was 84% (complete 56.5%, partial 27.5%). Overall 5-year survival for the whole group was 39%, and median survival time was 26 months. ConclusionA high response rate can be achieved in very elderly NHL patients despite aggressive histology, poor prognostic features, and reduced doses of chemotherapy. Age alone should not be a contraindication to treatment.

Secondary amyloidosis causing nephrotic syndrome in a patient with non-Hodgkin's lymphoma: quite a rare diagnosis

Secondary amyloidosis is usually a complication of chronic inflammation. Amyloidosis cases during the course of non-Hodgkin's lymphoma (NHL) are usually of AL-type, only one NHL patient with secondary amyloidosis has been reported. Our 79-year-old male patient visited us with multiple lymphadenopathies, and he was diagnosed with nodal marginal zone B-cell lymphoma. After four cycles of combined chemotherapy; his urea, creatinine levels started to increase and he developed nephrotic-range proteinuria. His rectal biopsy demonstrated amyloid deposition in submucosal vessel walls. The patient has been under hemodialysis for 10 months and his lymphoma is still in partial remission. We presented this case because it is the second NHL patient who developed secondary amyloidosis during his disease course.

Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies.

CD20 has proven to be an excellent target for the treatment of B-cell lymphoma, first for the chimeric monoclonal antibody rituximab (Rituxan™), and more recently for the radiolabelled antibodies Y-90 ibritumomab tiuxetan (Zevalin™) and I-131 tositumomab (Bexxar™). Radiation therapy effects are due to beta emissions with path lengths of 1–5 mm; gamma radiation emitted by I-131 is the only radiation safety issue for either product. Dose-limiting toxicity for both radiolabelled antibodies is reversible bone marrow suppression. They produce response rates of 70%–90% in low-grade and follicular lymphoma and 40%–50% in transformed low-grade or intermediate-grade lymphomas. Both products produce higher response rates than related unlabelled antibodies, and both are highly active in patients who are relatively resistant to rituximab-based therapy. Median duration of response to a single course of treatment is about 1 year with complete remission rates that last 2 years or longer in about 25% of patients. Clinical trials suggest that anti- CD20 radioimmunotherapy is superior to total body irradiation in patients undergoing stem cell supported therapy for B-cell lymphoma, and that it is a safe and efficacious modality when used as consolidation therapy following chemotherapy. Among cytotoxic treatment options, current evidence suggests that one course of anti-CD20 radioimmunotherapy is as efficacious as six to eight cycles of combination chemotherapy. A major question that persists is how effective these agents are in the setting of rituximab- refractory lymphoma. These products have been underutilised because of the complexity of treatment coordination and concerns regarding reimbursement.

Embryonal rhabdomyosarcoma tongue in a male child

We report a two and half years old male child, who at the age of 2 years developed a small 3 x 3 cm, reddish lesion on his right side of dorsum of tongue. There was a history of bleeding from the lesion, off and on. There was no family history of malignancy or history of exposure to radiation, etc to the child. Incision biopsy was done on July 2005 and the histological findings were consistent with an embryonal rhabdomyosarcoma. Parents of the child were reluctant for any further treatment. He was re-admitted in September 2005 with a massive growth over the tongue, protruding from the mouth [Figure 1]. The child was unable to close his mouth and was also unable to swallow solid food. He was accepting liquids only in small amounts. The growth was arising from the anterior part of tongue and extending up to the base of it. On examination, the growth was 8x6x10 cms, red, bosselated, with nodular ulcerated surface, well defined margins and was hard in consistency. Lower lip was ulcerated and compressed. There was no cervical lymphadenopathy. Other systemic examinations were normal. Skiagram of mandible and chest and ultrasonography of abdomen were normal. The patient was assigned a clinical stage 1 and international rhabdomyosarcoma study (IRS) Group III. Near total excision of mass was done [Figure 2]. Histopathological examination showed embryonal rhabdomyosarcoma. He received one cycle of combination chemotherapy (vincristine, actinomycin D & cyclophosphamide). The child is now able to swallow liquids as well as solids and he is on regular follow-up for chemotherapy and is doing well.

Nonleukemic Granulocytic Sarcoma in the Bile Duct: A Case Report

Granulocytic sarcoma (GS) is an extramedullary tumor composed of immature myeloid cells, typically occurring during the course of acute myelogenous leukemia. Nonleukemic GS, that is, GS with no evidence of overt leukemia and no previous history of leukemia, is very rare, and even more unusual is nonleukemic GS of the bile duct. We report a case of nonleukemic GS of the bile duct. The patient was initially misdiagnosed as a bile duct carcinoma arising in the hilum of the liver (so-called Klatskin tumor), and received a right lobectomy of the liver. Histological examination of the tumor yielded the diagnosis of GS, and the bone marrow biopsy did not show any evidence of leukemia. Considering the risk of subsequent development of overt leukemia, the patient was treated with two cycles of combination chemotherapy as used in the cases of acute myelogenous leukemia. To date, he has remained free of disease 15 months after treatment.

Evidence for Disease Specific Immunophenotypic Abnormalities in Blood from Patients with Mantle Cell Lymphoma.

Immune dysfunction is known to contribute to lymphomagenesis in the context of immunosuppressive therapy and infection with HIV. The current study was undertaken to test whether low grade but progressive forms of lymphoma, mantle cell lymphoma (MCL) and follicular lymphoma (FL), might be associated with systemic immunologic dysfunction as evaluated by flow cytometry. Because of recent studies suggesting a tumor initiating function for infiltrating macrophages in AIDS lymphoma (Zenger et al, Cancer Research 62:5536–42, 2002), we investigated the immunophenotype of both monocytes and T cells in blood from patients with recurrent MCL and FL. Heparinized blood was taken from 13 individuals with MCL and 6 with FL, both sets of patients previously treated with an average of 4 cycles of combination chemotherapy +/− Rituxan. No patient had received any therapy during the 3 months prior to the current study. Cell surface antigens CD14, CD16, HLA-DR, CD4, CD8, and CD38 were studied in the two diseases and results were compared to age matched controls. Blood from MCL patients showed an immunophenotypic pattern, similar to blood phenotypes described for patients infected with HIV. The %CD4 population was significantly lower than normal controls (p<0.05). The %CD8 T-cell population was elevated when compared to normal (p<0.001) as was the median level of CD38 expression on CD8 T-cells (p<0.01). The CD4/CD8 ratio was inverted (<0.85). Significant elevation of monocyte activation markers was observed in MCL blood when compared to normal controls. Mean fluorescence of HLA-DR on CD14+ cells was elevated (p<0.0001) as was the %CD14+ cells co-expressing CD16 (p<0.0003). By comparison, FL blood showed evidence for both CD4 and CD8 T cell activation with normal CD4/CD8 ratios, however there was no evidence for CD14 cell activation as observed in MCL blood. Taken together, these data suggest that MCL, as a lymphoma subset, shows significant evidence for systemic immune dysfunction and as an acknowledged T cell independent process, shows evidence for macrophage activation, shown recently to potentially play a role in AIDS lymphomagenesis. Further studies on MCL will be required to determine what “factors” might contribute to the persistently abnormal immunophenotype including investigating this class of lymphoma for viral like factors.

Clinical Study of Fludarabine, Mitoxantrone, and Dexamethasone in the Treatment of Refractory or Relapsed Multiple Myeloma.

BACKGROUND & OBJECTIVE: Until today, multiple myeloma is still an incurable malignancy by conventional therapy; it has low complete remission rate and high recurrence rate. Recurrence or relapse of the disease is almost inevitable for most of the patients after several cycles of combined chemotherapy. A safe and effective therapy for the treatment of relapsed and refractory multiple myeloma is urgently needed in clinical practice. This clinical study was designed to compare the safety and efficacy of the fludarabine-based regimen (fludarabine, mitoxantrone and dexamethasone [FMD]) with that of pirarubicin, vincristine and dexamethasone (VAD) in refractory or relapsed multiple myeloma.METHODS: The clinical data were retrospectively analyzed. The following indices were assessed before, during, and after the treatment in FMD-arm and VAD-arm: the partial remission (PR) rate, overall response (OR) rate, time to achieve PR, the number of patients and time to achieve the following: a decline in the serum M-component of more than 50% of the pre-treatment value, the ratio of myeloma cells in bone marrow drop to less than 50% of the pre-treatment value, the ratio of myeloma cells in bone marrow drop to less than 5% or drop more than 80% than pre-treatment level, the hemoglobin level increased more than 20 g/L, the white blood cell and platelet count of the peripheral blood, serum calcium, creatinine, β2-microglobin and ALT level, adverse events.RESULTS: The PR rate and OR rate are significantly higher in the FMD-arm than in the VAD-arm (PR rates were 46.2% vs 22.7% and OR rates were 61.5% vs 31.8%, P <0.05, respectively). The median time to achieve PR was 88 days in the FMD-arm, compared to 68 days in the VAD-arm (P <0.05). Approximately 40.0% of patients in the FMD-arm had >50% decrease in M-component or >20 g/L elevation in hemoglobin, compared to 22.7% and 18.2% in the VAD-arm respectively (P <0.05). The median times to achieve >50% decrease in M-component, decline of >80% of myeloma cells in the bone marrow than the pre-treatment level or ratio drop to less than 5%, or >20g/L elevation in hemoglobin were 62 days, 57 days, and 70 days, respectively. There were no significant differences between groups in serum calcium, creatinine, and ALT level pre-and post-treatment. The level of serum β2-microglobin was (1042.8±72.3 mg/L) post-treatment in the FMD-arm, which was lower than that observed before treatment (2350.2±184.0 mg/L; P <0.05). Most patients (76.9%) in the FMD-arm occurred III/IV grade leukocytopenia while 81.8% patient were I/II grade in the VAD-arm. The incidences of fever and cough were higher in FMD-arm comparing to VAD-arm (P <0.05). The progression free survival (PFS) on 1st and 2nd year and overall survival (OS) on 2nd year were 46.2%, 30.8% and 53.8% in the FMD-arm, while they were 50%, 27.3% and 40.9% respectively in the VAD-arm, which had no significant statistic difference (P >0.05).CONCLUSION: The PR rate and OR rate of FMD-arm are significantly higher than in the VAD-arm in the treatment of refractory or relapsed multiple myeloma, but it took longer time to achieve PR. The regimen of FMD shows no significant renal or hepatic toxicity, it's a safe and effective regimen in the treatment of refractory or relapsed multiple myeloma.