Aref Chehal

Hypertransfusion: A Successful Method of Treatment in Thalassemia Intermedia Patients With Spinal Cord Compression Secondary to Extramedullary Hematopoiesis

Summary of Background Data. Extramedullary hematopoiesis is a common compensatory phenomenon to chronic hemolytic anemias including thalassemia. Several sites can be involved including the liver, the spleen, the lymph nodes, and other less common locations. Spinal cord compression may result in the rare cases wherein the hematopoietic develops intraspinally. Treatment of such conditions still is controversial. Objective. This article reviews the literature and reports two cases of thalassemia intermedia involving patients who presented with neurologic symptoms after acute spinal cord compression secondary to extramedullary hematopoiesis. Methods. The diagnosis was established by magnetic resonance imaging. Hypertransfusion therapy was used as our first-line treatment method. Results. Complete neurologic recovery was achieved. Improvement in the neurologic status started as soon as the first week of treatment. Conclusions. Clinical awareness is important for early diagnosis and prevention of irreversible neurologic complications in such cases. Magnetic resonance imaging is the radiologic method of choice for diagnosing extramedullary hematopoietic masses and for delineating the extent of spinal cord involvement. Hypertransfusion seems to be a promising treatment method that should be recommended as a first-line approach or as an adjuvant therapy to other methods.

Transfusion‐associated GVHD: 10 years’ experience at the American University of Beirut—Medical Center

BACKGROUND: Although rare, transfusion‐associated GVHD (TA‐GVHD) is a fatal complication of blood transfusion in which active lymphocytes from the donor attack and destroy recipient organs and tissues.

Comparative Pharmacokinetics and Metabolic Pathway of Gemcitabine During Intravenous and Intra-arterial Delivery in Unresectable Pancreatic Cancer Patients

AbstractBackground: To study the pharmacokinetics and clinical outcome of gemcitabine (2′-2′-difluoro-deoxcytidine [dFdC]) during intra-arterial versus intravenous delivery in locally advanced and regionally metastatic pancreatic cancer. Patients and methods: Seven patients with unresectable pancreatic cancer received escalating intra-arterial doses of gemcitabine ranging from 800 to 1400 mg/m2, after selective embolisation of all pancreatic blood supply, except for the tumour-feeding arteries. Four patients received intravenous gemcitabine (control). Venous blood samples at different time intervals were taken throughout 270 minutes for pharmacokinetic analyses of gemcitabine and its inactive metabolite 2′-2′-difluorodeoxyuridine (dFdU). Results: Pharmacokinetic data revealed differences in plasma concentrations between intra-arterial and intravenous delivery routes. The plasma concentration-time curve of gemcitabine during and after cessation of intra-arterial pancreatic target administration through the proximal splenic artery showed a profile with an area under the plasma concentration-time curve from 0 to 270 minutes (intra-arterial 29.0 + 0.4 vs intravenous 331.0 + 2.7 ng · min/mL; p < 0.0001) and peak plasma concentration (intra-arterial 1.1 + 0.2 vs intravenous 7.6 + 2.0 ng/mL; p < 0.0001) significantly lower than that for the corresponding systemic intravenous route. A plot of In (% of dose) versus time showed a bi-compartmentalised metabolic model for intravenous administration of gemcitabine, one indicating rapid conversion of gemcitabine to dFdU, and another at a significantly lower affinity resulting in no conversion. Hence, this could be the main reason why dFdU was not detected in the systemic circulation during pancreatic intra-arterial target delivery. Furthermore, during intravenous administration a pseudo first-order rate constant (≈0.20 min-1) for in vivo conversion of gemcitabine to dFdU was estimated, indicating a rapid cellular deamination which was not shown in the intra-arterial route. Clinically, one patient had a partial response and six patients had a stable disease after intra-arterial administration of gemcitabine. The median time to disease progression was 4 months and the median overall survival was 5 months. One patient survived for 26 months. No grade III or IV toxicity was documented. Conclusion: Intra-arterial administration of gemcitabine has a major advantage related to reduced toxicity as increasing the dose through this administration route will eventually result in pancreatic cellular drug target delivery prior to systemic availability. Despite the low number of patients recruited, the clinical results are encouraging and this approach should be tested in a randomised study.

SICKLEMIA WITH MULTI-ORGAN FAILURE SYNDROME AND THROMBOTIC THROMBOCYTOPENIC PURPURA

Acute multi-organ failure syndrome is a rare and life-threatening complication of patients with sickle cell disease. The syndrome appears to be reversed with prompt, aggressive exchange transfusion therapy. It has been attributed to widespread vascular occlusion due to micro-vascular red cell sickling. We present a case of severe multi-organ failure in a patient with sickle thalassemia and mild clinical course, who had clinical and laboratory features consistent with thrombotic thrombocytopenic purpura (TTP). The dramatic response to therapy with plasma exchange, a treatment often effective in TTP, suggests a similarity in pathophysiology of micro-vascular occlusion and multi-organ failure in sickle cell disease.

β-THALASSEMIA INTERMEDIA AND NON-HODGKIN'S LYMPHOMA

The presenting symptoms of malignancies like anemia and splenomegaly in thalassemic patients can be overlooked and considered as complications of thalassemia. Our paper deals with a case of large B cell lymphoma with bone marrow involvement in an old lady with thalassemia intermedia. The patient showed complete response after the second cycle of chemotherapy that consists of cyclophosphamide, vincristine, and prednisone (CVP protocol). However, the patient relapsed with bone marrow involvement shortly after (2 weeks) completion of the sixth cycle of chemotherapy, and she was started on monoclonal antibodies Rituximab. On reviewing the literature, only four cases of thalassemia and lymphoma have been reported worldwide, thus making our case the fifth report of this rare combination of diseases.

Recurrent GI Bleeding and Surgery Following the Initial Response to Imatinib Therapy in GIST of the Stomach

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the GI tract. The concept of GIST and the definition of GIST pathology have evolved greatly over the past 5 years. They were formerly known as leiomyomas and leiomyosarcomas (1). Ongoing retrospective pathology reviews and immunologic stainings are awaited from several centers. Traditional treatment has been surgical resection but they usually recur and metastasize to liver and peritoneum. They rarely respond to chemotherapy or to radiation (2). Most GISTs have a mutation in the KIT proto-oncogene that translates into a gain-of-function, constitutive activation of the KIT kinase. KIT activation seems to be an early tumor-promoting event in pathogenesis (2). Selective tyrosine kinase inhibitors, like imatinib mesylate (formerly known as STI571), target this property and have become the standard therapy for metastatic or unresectable tumors (3). Ongoing research will determine optimal dosing and duration of Imatinib therapy. Evidence for resurgence of residual disease after tumor removal has recently been discussed in the literature (4, 5). We report a case of metastatic GIST that initially responded to imatinib and that recurred with GI bleeding and showed accelerated tumor growth after surgical resection.

A clinical phase II study of cisplatinum and vinorelbine (PVn) in advanced breast carcinoma (ABC).

Objectives:The effectiveness of cisplatinum and vinorelbine (PVn) as a salvage regimen in patients with metastatic breast cancer was reported in previous studies. This report is a pilot study assessing the antitumor efficacy and safety of this regimen as first line therapy for advanced breast cancer patients. Methods:Thirty-five patients were enrolled: 22 with metastatic breast carcinoma and 13 with locally advanced breast carcinoma (stage III). A total of 4 cycles of PVn were planned. After the 4th cycle, patients with metastatic breast cancer received vinorelbine biweekly until disease progression or for a total of 12 cycles, whereas those with locally advanced breast cancer who showed complete or partial response underwent curative surgery. Results:The overall response rate of our whole population was 74.29%. For the metastatic breast cancer group, the overall response rate was 64%, with a median survival of 19 months (range 2–36). For the locally advanced breast cancer group, the overall response rate was 92.3% with a median time to disease progression of 26 months (range 25–27). Toxicity was acceptable, and no treatment-related mortality was encountered. Conclusions:PVn is effective as first line treatment of advanced breast cancer with overall response rate of 64% in metastatic breast cancer and 92.3% in locally advanced breast cancer, and acceptable toxicity.

A clinical phase II study of a non-anthracycline sequential combination of cisplatin-vinorelbine followed by docetaxel as first-line treatment in metastatic breast cancer.

Background: We tested a sequential combination regimen using cisplatin and vinorelbine (PVn) followed by docetaxel as first-line chemotherapy in a phase II clinical trial in metastatic breast cancer (MBC). Patients and Methods: Thirty-five patients were enrolled. Cisplatin 80 mg/m2 was given on day 1 and vinorelbine 30 mg/m2 on days 1 and 8 every 3 weeks for 4 cycles. Responding patients received docetaxel 75 mg/m2 every 21 days for a maximum of 4 cycles. Three patients were excluded from analysis because of death unrelated to treatment. Results: After a median follow-up of 14 months, 32 patients completed the study. The overall response rate was 53.1%. Complete remission was seen in 5 patients (15.6%), partial response in 12 (37.5%), stable disease in 6 (18.75%), and progressive disease in 9 patients (28.1%). Median time to disease progression was 8 months (range 1–24). At 24 months, 12 (37.5%) patients were alive. A total of 183 cycles were administered. Febrile neutropenia was observed in 4 patients (2.2%). Grade II nephrotoxicity occurred in 12 cycles (6.5%) and grade III vomiting in 31/183 cycles (16.9%). Discussion: PVn is a feasible non-anthracycline option as first-line chemotherapy in patients with metastatic breast cancer and has acceptable toxicity. The sequential addition of 4 cycles of docetaxel following 4 cycles of PVn did not improve the overall response rate and results.

Hb H Disease and Multiple Myeloma

BALISTRAZZI P, 1985, BLUT, V50, P55; BERING HA, 1984, CLIN RES, V32, pA304; Chehal A, 2002, HEMOGLOBIN, V26, P219, DOI 10.1081-HEM-120015025; DASGUPTA A, 1988, AM J HEMATOL, V28, P130; DASH S, 1986, JPN J MED, V25, P57; Fabris P, 1977, Haematologica, V62, P629; Kaloterakis A, 2001, HAEMATOLOGIA, V31, P153, DOI 10.1163-15685590152492963; KAPLAN J, 1984, BLOOD, V64, P308; MINIERO R, 1985, HAEMATOLOGICA, V70, P78; MINIERO R, 1988, AM J HEMATOL, V27, P74, DOI 10.1002-ajh.2830270120; RUSSO A, 1987, AM J HEMATOL, V24, P111, DOI 10.1002-ajh.2830240115; STEVENS RG, 1988, NEW ENGL J MED, V319, P1047, DOI 10.1056-NEJM198810203191603; STRICKER RB, 1986, AM J HEMATOL, V21, P223, DOI 10.1002-ajh.2830210212; ZURLO MG, 1989, LANCET, V2, P27