Dipenkumar Modi

Incidence, Etiology and Outcome of Pleural Effusions in Allogeneic Hematopoietic Stem Cell Transplantation

Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity−mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 − 869) post‐HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 − 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P < 0.001). Overall, pleural effusion is a frequently occurring complication after allogeneic HSCT, adding to morbidity and mortality and hence, early identification is required. Am. J. Hematol. 91:E341–E347, 2016.

Multistate models on pleural effusion after allogeneic hematopoietic stem cell transplantation

A multistate model is more complicated than competing risk models and composed of finite number of states and transitions between states. Unlike competing risk models, this model has the ability to assess the effect of occurrence order of time-to-event data. Pleural effusion (PE) is a severe complication that often occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients develop pleural effusion during the first 100 days after allogeneic HSCT and graft-versus-host disease (GVHD) occurs either before or after the development of PE, implying that the occurrence order of PE and GVHD (i.e., PE after GVHD vs. GVHD after PE) would influence on the incidence, risk factors and mortality of pleural effusion. One can use either Cox proportional models or competing risk models to evaluate these values, but neither method is able to incorporate the occurrence order of incidence into the model. To resolve this difficulty, we developed a multistate model describing several possible events and event-related dependences and applied to a retrospective study of 606 patients, including eight covariates.

A phase II study of tacrolimus and thymoglobulin as graft-versus-host-disease prophylaxis in related donor allogeneic hematopoietic cell transplantation

Ayalew Tefferi , Sravanthi Lavu , Mythri Mudireddy , Terra L. Lasho, Christy M. Finke, Naseema Gangat , Animesh Pardanani, Curtis A. Hanson, Carmela Mannarelli, Paola Guglielmelli, Alessandro M. Vannucchi Division of Hematology, Mayo Clinic, Rochester, Minnesota Division of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota Department of Experimental and Clinical Medicine, CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi, University of Florence, Florence, Italy

Malignant cause of abdominal pain in leukemia: spontaneous splenic rupture.

S pontaneous splenic rupture (SSR) is a devastating etiology of acute abdomen in hematological malignancies. It is rarely associated with leukemia. Overall incidence of splenic rupture in leukemia is extremely low. Most of the cases had been reported in untreated cases of leukemia. Here, we describe the first case of a patient who had allogeneic stem cell transplantation (SCT) for secondary leukemia and about 45 days after the transplantation, he developed subacute presentation of acute abdomen secondary to splenic hematoma from leukemic splenic infiltrates, nonresponsive to therapeutic embolization which progressed into multiorgan failure. Our patient was a 66-year-old man who presented with left-sided abdominal pain of 6 days duration. The patient was diagnosed with myelodysplastic syndrome with high-risk cytogenetic abnormalities (inversion 3, monosomy 7, RPN1) and 6% blasts on bone marrow biopsy. Soon after diagnosis, he was treated with 1 cycle of decitabine, which was complicated by neutropenic fever requiring hospitalization and discontinuation of therapy. Repeat bone marrow biopsy showed 20% blasts concerning for development of acute myeloid leukemia (AML). He had undergone allogeneic hematopoietic SCT (10/ 10 matched unrelated donor peripheral blood SCT) for secondary AML 45 days before presentation. A reduced intensity conditioning preparative regimen of busulfan and fludarabine was used. He had received 17.55 3 106 CD34 cells per kilogram. Filgrastim (480 mcg daily; 4 mcg

Radium-223 in Heavily Pretreated Metastatic Castrate-Resistant Prostate Cancer

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Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT

d21) was given for 16 days after SCT to help with posttransplantation engraftment. Mycophenolate and tacrolimus along with 1 dose of thymoglobulin were started for graft versus host disease prophylaxis. A bone marrow biopsy 40 days after transplantation had shown 2% myeloblasts. The patient also had significant coronary artery disease with 3 previous myocardial infarctions with the last being 3 months before the current presentation. The abdominal pain had started insidiously and was radiating to the left shoulder. He did not report lightheadedness, recent infections or trauma. On presentation, vitals were normal. Physical examination was remarkable for distended tender abdomen without any guarding or rigidity and marked hepatosplenomegaly (liver span of 17 cm and tip of the spleen palpable up to umbilicus). Laboratory findings revealed hemoglobin of 7.9 g/dL and platelets 34,000/mm3, which were unchanged from his previous blood counts. Computed tomography (CT) scan of abdomen revealed markedly enlarged spleen measuring 25 cm. The patient was treated conservatively with analgesics and hydration. On day 6, his hemoglobin acutely dropped to 6 g/dL accompanied by hypoxia and hypotension. Serum troponin I was undetectable. Transthoracic echocardiogram showed normal left ventricular ejection fraction and normal collapsibility of inferior vena cava. Repeat CT abdomen revealed free peritoneal fluid and markedly enlarged spleen measuring 27 cm with ill-defined anterior margin studded with clots, consistent with splenic rupture with intraperitoneal hemorrhage (Figure 1A). He was deemed very high risk for surgical mortality with splenectomy because of significant coronary artery disease and fairly recent myocardial infarction as well as current hemodynamic instability. Hence, splenic artery embolization was performed as a temporizing measure to allow resuscitation and possible stabilization of hemodynamic status. Despite embolization, his clinical status rapidly deteriorated with development of multiorgan failure and acute respiratory distress syndrome requiring mechanical ventilation. At that point, surgical intervention was deemed extremely high risk with minimal, if any, potential benefit. Eventually, he died to multiorgan failure. Autopsy showed hemoperitoneum, enlarged spleen (4190 g) and liver (2850 g) and splenic congestion with widespread infarction due to embolization. Immunohistochemical stain of the spleen sections confirmed infiltration with myeloblasts positive for CD34 expression (Figure 1B). SSR is a rare complication of AML. Although splenomegaly is reported in context of granulocyte colony stimulating factor (G-CSF) use (for stem cell mobilization in patients and healthy donors as well as for engraftment), splenic rupture with G-CSF use is extremely rarely associated. Mechanisms responsible are infiltration of the spleen by leukemic cells leading to distortion of the splenic architecture, splenic infarction with subcapsular hemorrhage and capsule rupture. Risk factors for SSR in patients with hematologic malignancies include adult age, male sex, severe splenomegaly and previous or present use of G-CSF. Abdominal pain is the most common presenting symptom, which is usually acute and may be accompanied by lightheadedness. However, an absence of abdominal pain does not exclude the diagnosis since approximately one-third of the patients do not have abdominal pain or it is insidious in onset. Physical examination clues to the diagnosis are frank or orthostatic hypotension, abdominal tenderness and distension. Although splenomegaly is present in most of the patients, its absence does not exclude the diagnosis as about one-third of the patients do not have a palpable spleen. Abdominal ultrasound is usually the first radiologic modality used but is nondiagnostic in up to 30% of the cases. CT abdomen is overall the best diagnostic test. Splenectomy is the treatment of choice; however, many patients are not the candidates for it because of hemodynamic instability, and underlying coagulopathy. Irradiation of the rupture site or embolization of the splenic artery is an alternative therapeutic intervention in such cases. Our patient had splenic rupture from refractory AML. This complication is rare but should be considered as a cause of new onset abdominal pain in patients with refractory disease. Furthermore, subacute presentation of splenic rupture is frequently misdiagnosed as more benign etiologies such as gastritis, peptic ulcer disease or nephrolithiasis. The diagnosis is often challenging because of the absence of any history of trauma, initially stable vital signs and absence of frank splenomegaly on examination. The physicians should be aware of the importance of maintaining a high index of suspicion for this condition, especially in patients at high risk and not to exclude the diagnosis on the basis of seemingly benign physical examination findings as mortality approaches 100% in untreated cases.