Intermittent Low Dose Interleukin 11 Can Lead to Transfusion Independence in Patients with Chronic Myelo-Monocytic Leukemia and Thrombocytopenia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3939-3939
Author(s):  
Chirag Shah ◽  
Teresa C. Gentile

Recombinant Interleukin- 11 (IL-11) is a thrombopoietic cytokine that stimulates megakaryocytopoiesis in vitro and platelet production in vivo. It attenuates post chemotherapy thrombocytopenia at a dose of 50 mcg/ kg/ day subcutaneously (SC). Unfortunately, prolonged administration is associated with significant toxicity including peripheral and pulmonary edema at this dose. Administration of low dose IL-11 at 10 mcg/kg/day SC has shown efficacy in bone marrow failure states without significant toxicity. We report two cases of chronic myelo-monocytic leukemia (CMML) with transfusion dependent thrombocytopenia who received intermittent low dose IL-11 without significant toxicity. Case Reports- Patient 1 is a 79-year-old male with history of CMML with pancytopenia of three years duration. Recently he required transfusion of platelets with his platelet counts falling to less than 15 x 109/L. His cytogenetic study showed normal karyotype, 46 XY. He required platelet transfusion at every 14 days. He initially was started on IL-11 at 10mcg/kg/day, 5 days per week.. His platelet count increased to above 30 x 109/L and he became transfusion independent within two weeks. Unfortunately on this schedule he developed edema and mild CHF. IL-11 was stopped for two weeks and upon resolution of toxicity, restarted at 10 mcg/kg/day on Monday, Wednesday and Friday. He has remained transfusion independent without recurrence of edema at 5 months on this schedule. Patient 2 was a 63-year-old male with previous history of chronic lymphocytic leukemia and diffuse large B cell lymphoma who developed CMML with severe pancytopenia. His karyotype was 46, XY, −7, +21. His platelet count was consistently less than 10 x 109/L. He required platelet transfusion twice a week. He was started on IL-11 at 10mcg/kg/day for 5 days per week, two weeks on and two weeks off. His platelet count increased to as high as 64 x 109/L after 2nd cycle. His platelet transfusion requirement decreased from every 3rd day to every 10th-14th day. He experienced no peripheral or pulmonary edema. Conclusion: Administration of low dose IL-11 in other bone marrow failure states has been reported but its use has not been described in CMML. Our observation in these 2 patients suggests that IL-11 has efficacy in CMML and is very well tolerated at low doses on an intermittent administration schedule. IL-11 may decrease the transfusion requirement in transfusion dependent patients. Further studies are needed to evaluate overall impact on larger number of patients who require regular platelet transfusion.

2001 ◽  
Vol 19 (21) ◽  
pp. 4165-4172 ◽  
Author(s):  
Razelle Kurzrock ◽  
Jorge Cortes ◽  
Deborah A. Thomas ◽  
Sima Jeha ◽  
Susan Pilat ◽  
...  

PURPOSE: Interleukin-11 (IL-11) is a thrombopoietic cytokine that attenuates postchemotherapy thrombocytopenia at doses of 50 μg/kg/d subcutaneously. Very little is known about the activity of IL-11 in patients with bone marrow failure states. PATIENTS AND METHODS: Our preliminary experience with IL-11 at doses of 50 μg/kg/d suggested that patients with bone marrow failure developed significant peripheral and pulmonary edema after the prolonged dosing necessary for treating these conditions. We, therefore, initiated a study of low-dose IL-11 (starting dose, 10 μg/kg/d). RESULTS: Sixteen patients were assessable for response. Six patients had diploid cytogenetics; the others had a variety of chromosomal abnormalities. Six (38%) of 16 patients showed a platelet response to IL-11, and two had a multilineage response (to IL-11 alone, n = 1; to IL-11 plus G-CSF and erythropoietin, n = 1). The median increase in peak platelet counts was 95 × 109/L above baseline in the responders (range, increase of 55 × 109/L to 130 × 109/L above baseline). Responders included five of 11 patients with myelodysplasia and one of four patients with aplastic anemia. Response durations were 12, 13, 14+, 25, 30, and 30+ weeks. Side effects of IL-11 were mild (peripheral edema, n = 7; conjunctival injection, n = 7; myalgia, n = 1; all grade 1). Seven patients had no side effects. CONCLUSION: Our pilot study suggests that administration of low-dose IL-11 (10 μg/kg/d) can raise platelet counts without significant toxicity in selected thrombocytopenic patients with bone marrow failure.


2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2538-2538
Author(s):  
R. Kurzrock ◽  
I. Khouri ◽  
C. Bueso-Ramos ◽  
F. Giles ◽  
S. Pilat ◽  
...  

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2538-2538
Author(s):  
R. Kurzrock ◽  
I. Khouri ◽  
C. Bueso-Ramos ◽  
F. Giles ◽  
S. Pilat ◽  
...  

2005 ◽  
Vol 16 (1) ◽  
pp. 139-145 ◽  
Author(s):  
A.-M. Tsimberidou ◽  
F.J. Giles ◽  
I. Khouri ◽  
C. Bueso-Ramos ◽  
S. Pilat ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3703-3703
Author(s):  
Kazuhiko Ikeda ◽  
Tsutomu Shichishima ◽  
Kazuko Akutsu ◽  
Yukio Maruyama

Abstract PNH is an acquired hematologic disorder which is characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. Also, PNH is one disorder of bone marrow failure syndromes, including aplastic anemia (AA) and myelodysplastic syndrome (MDS). It is well known that immunologic mechanisms by cytotoxic T lymphocytes (CTLs) contribute to pathophysiology of these disorders. In fact, some reports (Maciejewski et al, Blood, 2001; Shichishima et al, Blood, 2002) showed that HLA-DR*1501 is related with clinical pathophysiology of PNH. In this study, to clarify significance of CD8+ CTLs in pathophysiology of PNH, we investigated HLA class I (A and B) alleles in Japanese patients with PNH (female: male=7:17), AA (female: male=14:15), and MDS (female: male=6:16) by high-resolution method using polymerase-chain reaction after obtaining informed consent and approval from the institutional Human Research Committee. Mean age ± standard deviation of PNH, AA, and MDS patients was 52 ± 16, 54 ± 20, and 59 ± 18, respectively. HLA genotyping showed that the frequency of HLA-A*0206 allele in PNH patients (22.9%) was significantly different from those in 309 unrelated Japanese individuals (Saito et al, Tissue Antigens, 2000) (7.7%; p<0.02) and AA patients (5.2%; p<0.01). In contrast, we found no significant differences in the frequencies of the other alleles between PNH, AA, or MDS patients and the controls or between these disorders, except for high frequency of HLA-B40 alleles in AA patients (Nakamura et al, Blood, 2003). Then, various clinical parameters, including peripheral blood, bone marrow blood, and laboratory findings, proportions of glycosylphosphatidylinositol protein-negative population in erythrocytes, granulocytes, and monocytes, findings of chromosomal analyses and HLA-DR alleles, transfusion requirements, past history of AA, and history of thrombosis, were statistically compared between HLA-A*0206-positive group (n=10) and -negative group (n=14) in PNH patients. Statistical analyses showed that the reticulocyte counts , the values of lactate dehydrogenase, and the frequency of PNH patients with over 30% of CD59− erythrocytes in HLA-A*0206-positive group were significantly higher than in HLA-A*0206-negative group (121 ± 49 x 109/L vs 76.9 ± 43.9 x 109/L, p<0.03; 2866 ± 2606 IU/L vs 938 ± 775, p<0.02; and 80.0 % vs 28.6 %, p<0.02, respectively). Moreover, we found no AA (n=3) and MDS (n=5) patients with both the HLA-A*0206 allele and more than 1% of CD59− granulocytes. In conclusion, our findings suggest that the HLA-A*0206 allele in PNH may be correlated with the grade of the disease by complement-mediated hemolysis during negative selection of PNH clones, probably due to immunologic mechanisms by CD8+ CTLs.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5238-5238 ◽  
Author(s):  
Samuel A. Jacobs ◽  
Barry McCook ◽  
Frank Torok ◽  
Norbert Avril ◽  
Nick Vidnovic ◽  
...  

Abstract Background: As the first radioimmunotherapeutic (RIT) agent approved for the treatment of relapsed or refractory B-cell NHL, yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) has been shown to achieve durable responses in heavily pretreated NHL patients. In phase 1–2, the eligibility criteria for 90Y ibritumomab tiuxetan therapy excluded patients with hypocellular bone marrow (<15%), lymphomatous involvement >25%, or prior ASCT due to concern of depleting the bone marrow reserve. However, Kaminski et al previously demonstrated that a parallel RIT agent, 131I tositumomab, was safe and efficacious when administered after ASCT (Blood2000; 96:1259–66). We report our experience of using ibritumomab tiuxetan in NHL patients with a prior history of ASCT. Methods: Patients with histologically confirmed relapsed or refractory B-cell NHL, ≥18 years, platelet counts >100,000/mm3, bone marrow cellularity >15%, and lymphomatous involvement <25% were eligible for treatment. In a series of 40 patients treated with ibritumomab tiuxetan at the UPMC Cancer Center, 6 patients with prior ASCT were treated. A standard course of ibritumomab tiuxetan was given, with the therapeutic dose of 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (the initial patient, and another with platelet count ≥150,000/mm3) or the standard dose of 0.4 mCi/kg 90Y in the 4 remaining cases (baseline platelet count >150,000/mm3). Pretreatment diagnostic PET/CT scans were taken for all patients and evaluated for areas of lymphomatous involvement. Follow-up scans were performed approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored weekly over a 12-week period after therapy and classified according to CTCAE v. 3.0 toxicity criteria. Results: Patients with a prior history of ASCT had received a minimum of 4 previous regimens (range, 4–7). Subjects presented with follicular NHL (n = 3), transformed NHL (n = 1), large cell lymphoma (n = 1), and mantle cell lymphoma (n = 1). Six patients were evaluable for toxicity and 5 patients were evaluable for response. Observed toxicities were consistent with those expected in this patient population, with 33% (2/6) and 17% (1/6) of patients experiencing grade 4 thrombocytopenia and grade 3 neutropenia, respectively. Episodes of bleeding or neutropenic fever were not observed. Of the 5 patients evaluable for response, 1 patient with follicular lymphoma had a complete response to ibritumomab tiuxetan as determined by FDG-PET imaging. Conclusions: Ibritumomab tiuxetan therapy is feasible and safe in NHL patients who have previously received ASCT. Heavily pretreated patients can benefit from the administration of ibritumomab tiuxetan although additional data are needed to further characterize the degree of clinical response after ASCT.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4264-4264
Author(s):  
Chandrika Sreekantaiah

We report a recurrent translocation (X;20)(q13;q13.3) in three patients. The translocation was the sole chromosomal abnormality in all three patients and the number of cells with the abnormality varied from three to seventeen out of twenty metaphases analyzed for each patient. The patients were all female with ages ranging from 66 to 83. The presenting symptoms were variable but all included a history of anemia. Bone marrow aspiration showed acute monocytic leukemia in one patient and normocellular bone marrow with no detectable morphologic or immunophenotypic evidence of neoplasm in the other two. Only eight cases with the translocation have previously been reported. Seven of these cases had either myelodysplastic syndrome or acute myeloid leukemia and one patient had pancytopenia of unknown etiology. Repeated bone marrow evaluations on this patient showed no dyspoietic changes. The t(X;20) has clearly been established as a nonrandom abnormality, however, the clinical significance of the translocation is not clear. Close follow up of these patients is therefore essential. Characterization at the molecular level will also help to determine the genes involved and the mechanism of their action.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5009-5009
Author(s):  
Nassim Nabbout ◽  
Mohamad El Hawari ◽  
Thomas K. Schulz

Abstract Abstract 5009 Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells that can result in osteolytic bone lesions, hypercalcemia, renal impairment, bone marrow failure, and the production of monoclonal gammopathy. The gastrointestinal tract is rarely involved in myeloma. GI polyposis is a rare manifestation of extra-medullary disease in multiple myeloma. Such cases usually present as gastrointestinal hemorrhage or intestinal obstruction. A 53-year-old African American male recently diagnosed with multiple myeloma presented with three-day history of rectal bleed and fatigue. EGD showed multiple raised, polypoid, rounded lesions with a superficial central ulceration in the stomach. Colonoscopy showed similar lesions in the ascending and transverse areas of the colon that ranged in size from 5 to 16 mm in diameter. Biopsies showed that these polyps were made of plasma cells. A bone marrow biopsy showed diffuse involvement (greater than 90%) of bone marrow with multiple myeloma with anaplastic features. The patient was started on bortezomib at diagnosis, however, he passed away a few weeks later. This type of metastatic disease has been described in isolated case reports in the literature, while solitary GI plasmacytoma has been reported more frequently. In rare cases, multiple myeloma can involve the GI tract which may lead to bleed or obstruction. This involvement is likely a marker of aggressivity. This example of extra-medullary disease in myeloma is an uncommon variant with features of poor prognosis and dedifferentiation. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3518-3518
Author(s):  
Jennifer Anadio ◽  
Adam Lane ◽  
Cristina Tarango ◽  
Peter Sturm ◽  
Joseph S. Palumbo

Abstract Preoperative screening for bleeding disorders in pediatric patients is problematic due to children's limited exposures to significant hemostatic challenges and the inherent difficulty in obtaining blood samples from young patients. Overcoming these challenges is of particular importance for surgical procedures that carry a significant bleeding risk, such as spinal surgeries. Many pediatric surgeons, including the Pediatric Orthopedic team at our Institution, rely on an unfocused history and measurement of general markers of hemostasis for preoperative screening. In order to improve preoperative screening of pediatric patients undergoing spinal procedures, we instituted the use of a detailed semi-quantitative questionnaire based on the ISTH Bleeding Assessment Tool (BAT), in combination with evaluation of PT, aPTT, platelet count, and PFA. The BAT gives positive points for a personal or family history of bleeding, and negative points for significant hemostatic challenges that did not result in bleeding complications. It was decided a priori that a BAT score of ≥3 would result in referral to Pediatric Hematology. A total of 212 patients presenting for major spinal surgeries (e.g., spinal fusion, growth rod placement) ranging in age from 3 to 25 years were prospectively evaluated in this fashion. A total of 41 patients (19.3%) had a prolongation of the PT and/or aPTT, none of which had a high BAT score. The majority of the abnormal PT/aPTT values were minimal prolongations that were not reproducible on repeat testing. Prolongation of the PT and/or aPTT revealed 3 patients with mild deficiencies of either factors VII, X, or XI, none of which were felt to be clinically significant. Prolonged PFAs were observed in 32 patients (16%), 1 of which was diagnosed with type I VWD (BAT score = 1), and the other with "possible VWD" based on a borderline VWF antigen level (BAT score = 0). Both were treated with Humate P. The remainder of the patients with a prolonged PFA were determined not to have a significant bleeding disorder after further testing. A total of 15 patients were referred to Hematology based on a high BAT score. Of these, 2 had a history of thrombocytopenia (1 with known DiGeorge syndrome and 1 with Depakote-related thrombocytopenia). Neither required platelet transfusion. One patient with a high BAT score was known to have type I VWD and was treated with Humate P, another was diagnosed with low expression of glycoprotein GP1b and was treated with Humate P and platelet transfusion. The remainder of the patients with high BAT scores were not felt to have a clinically significant bleeding disorder based on a Hematologist's assessment. None of the 212 patients evaluated were felt to have excessive intraoperative bleeding by the surgical team, suggesting that none of the patients had a significant undiagnosed hemostatic defect. Together, these results suggest that reliance on history or screening labs alone may not be sufficient for many pediatric surgery patients. While the PFA identified 2 patients with mild/possible VWD that would have been missed by the BAT, the PFA also had a significant number of apparent false positives. The combination of a BAT and a platelet count, as well as assessment of VWF activity for patients without previous hemostatic system challenges, may provide a more effective screening methodology for institutions with ready access to VWF activity measurement. Disclosures No relevant conflicts of interest to declare.


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