Sandip Shah

A rare complication in a case of multiple myeloma on therapy with thalidomide and dexamethasone—Reversible posterior lobe leukoencephalopathy

Central nervous system involvement is an unusual manifestation of multiple myeloma. We report a case with a rare manifestation of multiple myeloma in the form of reversible white matter changes of occipital lobes presenting with blindness. This 45-year-old postmenopausal female presented to us (in March 2005) with complaints of lethargy, breathlessness on exertion and generalised bone pains of 3 – 4 months duration. General clinical examination was normal except presence of pallor and pedal edema. Systemic examination was also essentially normal except for presence of a threefinger palpable soft liver enlargement and a just palpable firm spleen. Investigations revealed the following picture: hemoglobin at 5 gm%, total leucocyte count of 5300 with a differential count of 60% polymorphs and 27% lymphocytes and no atypical cells, platelet count of 90000/c.mm. The ESR was 150 mm/hr. Biochemistry was normal except for a serum albumin level of 2.7 gm/dl and a globulin level of 5.3 gm/dl suggesting a reversed albumin/globulin ratio. Serum electrophoresis revealed a prominent monoclonal band. Quantitative serum immunoelectrophoresis revealed significantly high serum IgG levels of 2213 mg/dl (normal level1⁄4 650 – 1500 mg/dl) and a low IgM level of 50 mg/dl (normal level1⁄4 60 – 280 mg/dl). Serum beta-2-microglobulin level was normal (1.85 micro gm/ml). Ultrasound of the abdomen was suggestive of hepatomegaly with fatty infiltration and splenomegaly without alteration of echotexture. Bone marrow aspiration showed hypercellular marrow with infiltration by 95% atypical plasma cells. Conventional cytogenetic study showed normal XX karyotype. FISH study for deletion 13q was negative. Skeletal survey showed multiple punched out lytic lesions in bones. On routine screening, the patient was detected to be hepatitis B surface antigen positive. Considering the diagnosis as multiple myeloma stage III A, she was put on combination therapy with thalidomide and high dose dexamethasone every 28 days (thalidomide at a dose of 200 mg/day and dexamethasone at a dose of 40 mg/day from day 1 to day 4, day 9 to day 12 and day 17 to day 20 on even cycles and day 1 to day 4 only on odd cycles), along with cotrimoxazole prophylaxis and lamivudine for hepatitis B. After two such cycles she had a very good response with improvement in symptoms, resolution of anemia and thrombocytopenia with normalization of hemoglobin and platelets. Serum protein levels and electrophoresis became normal. Repeat quantitative immunoelectrophoresis was also normal. The dose of thalidomide was increased to 300 mg/ day in the third cycle. When she came for fourth cycle she was having sensory symptoms in lower limbs without evidence of motor weakness, suggestive of

Successful Allogeneic Hematopoietic Stem Cell Transplantation of a Patient Suffering from Type II Congenital Dyserythropoietic Anemia A Rare Case Report from Western India

The most frequent form of congenital dyserythropoiesis (CDA) is congenital dyserythropoietic anemia II (CDA II). CDA II is a rare genetic anemia in humans, inherited in an autosomally recessive mode, characterized by hepatosplenomegaly normocytic anemia and hemolytic jaundice. Patients are usually transfusion-independent except in severe type. We are here reporting a case of severe transfusion-dependent type II congenital dyserythropoietic anemia in a 5-year-old patient who has undergone allogeneic hematopoietic stem cell transplantation (HSCT) at our bone marrow transplantation centre. Patient has had up until now more than 14 mL/kg/month of packed cell volume (PCV), which he required every 15 to 20 days to maintain his hemoglobin of 10 gm/dL and hematocrit of 30%. His pre-HSCT serum ferritin was 1500 ng/mL and he was on iron chelating therapy. Donor was HLA identical sibling (younger brother). The preparative regimen used was busulfan, cyclophosphamide, and antithymocyte globulin (Thymoglobulin). Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis. Engraftment of donor cells was quick and the posttransplant course was uneventful. The patient is presently alive and doing well and he has been transfusion-independent for the past 33 months after HSCT.

Acquired severe aplastic anemia treated with antithymocyte globulin and cyclosporine: An experience of regional cancer center, Western India

Severe aplastic anemia (SAA) is a serious bone marrow disease that needs a comprehensive and service-intense treatment with either bone marrow transplantation (BMT) or immunosuppressive therapy (IST); both are difficult to optimally offer in resources-limited countries. Here, we report the outcome of IST using horse Antithymocyte globulin (ATG) in 18 (7 children; 11 adults) patients with SAA referred to our center in west India. Only 18 patients out of 102 diagnosed as AA in 2 years could receive IST, largely due to costs restraints. Although CR was seen in 30% in adults and 33% in pediatric cases, but overall 50% cases were able to enjoy transfusion-independence, requiring no further treatment. Treatment related mortality occurred in 6.2%, relapse in 6.2% and 6.2% had clonal evolution. This makes IST a valuable option for managing SAA in absence of bone marrow transplantation.

Aleukemic granulocytic sarcoma and leukemia cutis: A report of two rare cases and review of literature

Granulocytic sarcoma (GS), also called myeloid sarcoma is an extramedullary tumor of the immature granulocytic cells. It is a rare entity and mostly accompanied by acute myeloid leukemia (AML). Very rarely, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the GS is described as aleukemic, primary or isolated. Here, we report two rare cases, one of which presented as aleukemic GS of lymph nodes with aleukemic leukemia cutis, and the other with aleukemic GS of lung. Both cases posed diagnostic dilemma in view of their atypical presentations and site of involvement. Final diagnosis was made by immunohistochemistry (IHC). Both patients were treated with standard induction chemotherapy for AML. One patient had relapsed on treatment and was further treated with only 6-thioguanine leading to complete remission. Our cases emphasize the importance of early suspicion and use of IHC in diagnosis of aleukemic GS and also potential role of oral thioguanine alone in relapsed cases not eligible for hematopoietic stem cell transplant.

Experience of hematopoietic stem cell transplantation (HSCT) in the patients infected with either hepatitis B or hepatitis C virus

Background: Hematopoietic stem cell transplantation (HSCT) is challenging in Hbs-Ag positive or HCV-Ab positive patients due to fear of delaying engraftment and transplant-related mortality (TRM). Very few data are published internationally till date. We had done HSCT (allogenic/autologus) of 19 hepatitis B and hepatitis C positive malignant and nonmalignant patients at our institute during the years 1999–2013. Design and methods: We performed a retrospective analysis of the patients who were either hepatitis B or hepatitis C virus seropositive at the time of HSCT (n = 19). All the positive patients (Hbs-Ag positive or HCV-Ab positive) who underwent HSCT for malignant or nonmalignant causes during 1999–2013 were selected. A total of 13 patients underwent autologus HSCT and 6 patients underwent allogenic HSCT. All the included patients had performance score 1, normal liver function test, and noninfectious state of Hbe antigen before HSCT. Results: The median age of the seropositive patients was 25 years (range 7–54); 16 patients were Hbs-Ag positive and 3 were HCV-Ab positive. Most common indication of HSCT was lymphoma (n = 12), in which 7 patients were of Hodgkin disease and 5 patients were of non-Hodgkin disease (NHL). Three patients were acute myeloid leukemia, 2 patients of thalassemia major, 1 patient was of chronic myeloid leukemia-chronic phase, and 1 of multiple myeloma. We had used high-dose chemotherapy for induction with carmustine, etoposide, cytarabine, and melphalan (BEAM) for autologus HSCT and busulfan, cyclophosphamide (BUCY), busulfan, cyclophosphamide-thymoglobulin (BUCY-THYMO), and reduced intensity HSCT (RIST) for allogenic HSCT. All the patients underwent successful engraftment except one NHL patient. The median duration of neutropenia was 14 and 11 days in the allogenic HSCT and autologus HSCT, respectively. Median duration for engraftment of neutrophils was achieved on +Day 17 with 3 consecutive absolute neutrophil counts of more than 500 cumm/dL. Median duration for engraftment of platelets was achieved on +Day 19 with 3 consecutive platelet counts of more than 50,000 cumm/dL without any component support. Out of 6 allogenic HSCT patients, 4 developed graft versus host disease (GVHD) (2 – liver, 1 – colon, 1 – both skin and liver). Three patients died due to liver GVHD (2 – acute, 1 – chronic). Grades of GVHD in allogeneic HSCT patients are as follows, for liver (grade 3 in 2, grade 4 in 1), colon (grade 2 in 1), and skin (grade 2 in 1). Out of the 8 patients, one patient developed grade 3 veno-occlusive disease. Median at 100 days, 1-year overall survival (OS), and 5-year OS were 89.4%, 94.1%, and 81.1%, respectively. Conclusions: HSCT is a rugged job in Hbs-Ag positive or HCV-Ab positive patients due to more complications in the form of more neutropenia, GVHD, drug toxicity of chemotherapy, acute fulminant liver failure, fear of delaying of engraftment, and TRM. Careful evaluation before embarking on HSCT and intensive assessment against complications are warranted in Hbs-Ag positive and HCV-Ab positive recipients.

Primary Mediastinal Synovial Sarcoma Presenting as Superior Vena Cava Syndrome: A Rare Case Report and Review of the Literature.

Primary mediastinal sarcomas are aggressive tumors with a very rare incidence. This report describes the case of a 35-year-old male patient who presented with acute symptoms of dyspnoea, facial puffiness, voice-hoarseness, and engorged neck veins. With the clinical picture consistent with the superior vena cava (SVC) syndrome, the patient was investigated with computed tomography of the chest. This revealed a large soft tissue density mass lesion compressing the SVC along with other critical superior mediastinal structures. Histopathological evaluation of the mass revealed features consistent with a soft tissue sarcoma and positive staining was observed for vimentin and S-100. Cytogenetic analysis by fluorescent in situ hybridisation (FISH) demonstrated the t(X:18) translocation. Thus diagnosis was established as primary mediastinal synovial sarcoma. Patient was treated with three cycles of neoadjuvant chemotherapy, to which there was a partial response as per the RECIST criteria. Surgical excision of the mediastinal mass was performed, and further postoperative treatment with adjuvant chemoradiotherapy was provided. Patient currently is free of disease. This is to the best of our knowledge the first report in the world literature of a successfully treated case of “primary mediastinal sarcomas presenting as SVC syndrome.” Patient is under regular surveillance at our clinic and remains free of recurrence one year after treatment completion.

Primary Extraskeletal Ewings Sarcoma of Ala of Nose.

Extra skeletal Ewings sarcoma is often described as a tumour involving the soft tissues of the lower extremities and the para vertebral region. Ewings sarcoma presents a rare tumour of the head and neck, and even rarer in the nasal cavity and/or paranasal sinuses. Primary Ewing’s sarcoma of the ala of the nose has not been commonly described previously in the English literature. We present a case of primary Ewings sarcoma of the nose in a 23-year-old male, presented as a fleshy mass in the ala of the left side of the nose with symptoms of nasal obstruction. The obstructing lesion was excised and microscopy showed a neoplasm composed of comparatively uniform undifferentiated cells forming solid nests. The cytoplasm of the cells was clear but poorly demarcated, partly vacuolated and contained much glycogen. The cells expressed the MIC2 gene (using the CD99 marker). Managed with wide local excision and all resection margins are microscopically free of tumour margins. Post-operative adjuvant chemotherapy was started with High-Risk protocol (vincristine, doxorubicin, cyclophosphamide and mesna alternating every 3 weeks combined ifosfamide and etoposide) and is under follow up. An extensive review of literature, to the best of our knowledge, did not reveal many cases of EES of ala of nose.

The treatment of chronic myeloid leukemia, data from Gujarat Cancer and Research Institute, Ahmedabad

Gujarat Cancer and Research Institute, Ahmedabad presented data of total 840 patients, out of which 775 (90%) were in chronic phase. Complete hematological response (CHR) was seen in 96% of patients and median time to achieve (CHR) was 2 months. Complete cytogenetic response was seen in 36%.