We evaluated the outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced intensity conditioning (RIC). Median age at HCT was 55 years. Donors were: matched sibling donor (MSD), 34%; HLA-well-matched unrelated donors (URD), 45%; and partially/mismatched URD, 21%. Risk stratification according to Dynamic International Prognostic Scoring System (DIPSS): low, 12%; intermediate-1, 49%; intermediate-2, 37%; and high, 1%. The probability of survival at 5-years was 47% (95% CI 40–53). In a multivariate analysis, donor type was the only independent factor associated with survival. Adjusted probabilities of survival at 5-years for MSD, well matched URD and partially matched/mismatched URD were 56% (95% CI 44–67), 48% (95% CI 37–58), and 34% (95% CI 21–47), respectively (p=0.002). Relative risks (RR) for NRM for well-matched URD and partially matched/mismatched URD were 3.92 (p=0.006) and 9.37 (p<0.0001), respectively. A trend towards increased NRM (RR 1.7, p=0.07) and inferior survival (RR 1.37, p=0.10) was observed in DIPSS-intermediate-2/high-risk patients compared to DIPSS-low/intermediate-1 risk patients.
RIC HCT is a potentially curative option for patients with MF, and donor type is the most important factor influencing survival in these patients.
Myelofibrosis; allogeneic transplantation; reduced intensity; prognosis
Sialendoscopy; Sialolithiasis; Salivary gland; Stenson’s duct; Wharton’s duct
Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus-host disease (GVHD) in adults with acute leukemia who survived at least one year after allogeneic HCT is difficult. We analyzed 3339 patients with acute myeloid leukemia (AML) and 1434 with acute lymphoblastic leukemia (ALL) who received myeloablative conditioning and related or unrelated stem cells from 1990–2005. Most clinical factors predictive of LFS in one year survivors were no longer significant after two or more years. For AML, only disease status (beyond first complete remission) remained a significant adverse risk factor for LFS two or more years after transplantation. For ALL, only extensive chronic GVHD remained a significant adverse predictor of LFS in the second and subsequent years. For patients surviving for one year without disease relapse or extensive chronic GVHD, the risk of developing extensive chronic GVHD in the next year was 4% if no risk factors were present, and higher if non-cyclosporine-based GVHD prophylaxis, an HLA-mismatched donor, or peripheral blood stem cells were used. Estimates for subsequent LFS and extensive chronic GVHD can be derived for individual patients or populations using an online calculator (http://www.cibmtr.org/LeukemiaCalculators). This prognostic information is more relevant for survivors than estimates provided before transplantation.
leukemia-free survival; chronic graft-versus-host disease; landmark analysis; survivorship; prognosis
Trichobezoars are rarely described in the absence of trichotillomania. In this report we present a case of trichobezoar associated with trichophagia in the absence of trichotillomania. A 16-year-old girl presented to surgery outpatient with complaints of pain in abdomen and vomiting for the last 6 months. Physical examination revealed a 14 × 16 cm firm, tender, mass with smooth surface, irregular margins, which was mobile with respiration. Ultrasound abdomen revealed a bizarre lesion in the right upper and middle abdomen suggestive of gastric bezoars. Upper gastrointestinal endoscopy did not reveal any abnormality in the esophagus and showed a large mobile mass in the stomach. In view of trichobezoar, psychiatry consultation was sought. Exploration of history revealed that the patient was eating hairs and clay since early childhood. As per patient she would eat hairs thrown by others. She would like the taste of hair and had strong persistent desire to eat hair and would go out searching for the same. At times she would also eat clay. However, she denied of pulling her own hairs. Physical examination of scalp and other body parts did not show any evidence of alopecia or pulling of hair/short hair. She was managed surgically and was counseled about the consequences of eating hairs and clays and was encouraged not to eat hair. To conclude our case suggests that patients can have trichobezoar and trichophagia even in the absence of trichotillomania.
Trichophagia; trichotillomania; trichobezoar
CD3+CD56−, CD4 and CD8 double negative T (DNT) cells comprise 1–3% of peripheral blood mononuclear cells. Their role in tumor immunity remains largely unknown due to their limited numbers and lack of effective methods to expand them. Here we developed a novel protocol by which DNT cells can be expanded ex vivo to therapeutic levels in 2 weeks from 13 of 16 acute myeloid leukemia (AML) patients during chemotherapy-induced complete remission. The expanded DNT cells expressed similar or higher levels of IFN-γ and TNF-α, and Granzyme B as that seen in bulk activated CD8 T cells from the same patient but significantly higher levels of perforin. The expanded DNT cells could effectively kill both allogeneic and autologous primary CD34+ leukemic blasts isolated from peripheral blood of AML patients in a perforin-dependant manner. These results demonstrate, for the first time, that DNT cells from AML patients can be expanded ex vivo even after intensive chemotherapy, and are effective at killing both allogeneic and autologous primary leukemic blasts. These findings warrant studies further exploring the potential of DNT cells as a novel adjuvant immunotherapy to decrease the risk of relapse in patients with AML and, perhaps other cancers.
Acute Myeloid Leukemia (AML); Double Negative T (DNT) cells; Adoptive Immunotherapy
The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Ph+ acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type, and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKI), mostly imatinib; 39% (RIC) and 49% (MAC) were MRDneg pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%;p=0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (p=0.058). Overall survival was similar (RIC 39% [95% CI:27–52] vs. 35% [95% CI:270–44];p=0.62). Patients MRDpos pre-HCT had higher risk of relapse with RIC versus MAC (HR 1.97;p=0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared to a similar MRDneg population after MAC (33%; p=0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; p=0.057), but absence of pre-HCT TKI (HR 1.88;p=0.018), RIC (HR 1.891;p=0.054) and pre-HCT MRDpos (HR 1.6; p=0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRDneg status is preferred pre-HCT.
Acute lymphoblastic leukemia; Philadelphia chromosome; reduced intensity conditioning; allograft; minimal residual disease; tyrosine-kinase inhibitor
The survival of relapsed acute myeloid leukemia (AML) after autologous hematopoietic stem cell transplantation (Autologous HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (Allo-HCT) from an unrelated donor (URD) using either myeloablative (n=242) or reduced-intensity conditioning regimens (RIC, n=60) reported to CIBMTR. After a median follow-up of 58 months (range 2–160), the probability of treatment-related mortality (TRM) was 44% (95%CI 38–50) at 1-year. The 5-year incidence of relapse and overall survival (OS) was 32% (95%CI 27–38) and 22% (95%CI 18–27), respectively. In multivariate analysis significantly better OS was observed with RIC regimens (Hazard Ratio (HR) 0.51, 95%CI 0.35–0.75, p<0.001), with Karnofsky performance status (KPS) ≥90% (HR 0.62, 95%CI 0.47–0.82, p=0.001) and in CMV-negative recipients (HR 0.64, 95%CI 0.44–0.94, p=0.022). Longer interval (>18 months) from Autologous HCT to URD Allo-HCT was associated with significantly lower Relapse risk (HR 0.19, 95%CI 0.09–0.38, p<0.001) and improved LFS (HR 0.53, 95%CI 0.34–0.84, p=0.006). URD Allo-HCT after Autologous HCT relapse results in 20% long-term leukemia-free survival, with best results with longer interval to secondary URD transplantation, KPS ≥90%, in complete remission, and using RIC regimens. Further efforts to reduce TRM and relapse are still needed.
AML; Unrelated Donor; Transplantation; Allogeneic; Autologous
Cutaneous infections caused by atypical mycobacteria are uncommon and the diagnosis can be missed unless there is strong clinical suspicion supported by laboratory confirmation. We report a case of chronic discharging sinus caused by Mycobacterium fortuitum in a young healthy immunocompetent individual. The patient recovered completely following amikacin and ofloxacin therapy.
Cutaneous infection; immunocompetent; Mycobacterium fortuitum
Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100–200 × 109/l, >200 × 109/l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan–Meier method according to original randomization group. In ruxolitinib-treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I.
Myelofibrosis; ruxolitinib; subgroups; spleen volume; symptoms
Iatrogenic perforation of the bowel is a rarity and no case has been reported in the literature so far, of iatrogenic ileal perforation due to orthopaedic guide wire insertion while doing open reduction and internal fixation of fracture neck of femur. As the number of these fixation procedures is increasing by the day it is imperative that surgeons remain aware of this potential complication and take pre-emptive measures to prevent it.
Iatrogenic; Ileal perforation; Fracture neck of femur
Allogeneic stem cell transplantation is the most effective treatment option for many hematological malignancies, but graft-versus-host-disease (GvHD) remains a major cause of treatment failure. Besides well established risk factors for the outcome of transplantation, recent single-center studies have identified a birth order effect in HLA-identical sibling stem cell transplantation with lower incidence of acute and chronic extensive graft-versus-host disease (aGvHD/cGvHD) and improved overall survival when a donor is younger than the recipient. One hypothesized mechanism is microchimerism due to fetomaternal and transmaternal sibling cell trafficking during pregnancy as the donor is exposed to recipient antigens in utero.
Design and Methods
The aim of this study was to validate single-center data in a multicenter cohort provided by the Center for International Blood and Marrow Transplantation (CIBMTR). All adult and pediatric patients (n=11,365) with a diagnosis of a hematologic malignancy receiving an allogeneic stem cell transplantation from an HLA-identical sibling donor from 1990 to 2007 were included.
When donors were younger than recipients, there was a significantly lower aGvHD II-IV° and cGvHD rate for children as well as lower cGvHD rate for adolescents. However, the hypothesized overall positive effect of lower relapse and better survival when donors are younger than recipients was not observed in this large multicenter study.
Our data suggest that if otherwise equally matched, a graft from a sibling younger than the patient may be superior to an older one for child and adolescent stem cell transplant patients.
allogeneic hematopoietic cell transplantation; birth order; HLA-identical sibling donors
Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment, albeit in a minority of patients with accelerated (AP) or blast phase (BP) chronic myeloid leukemia (CML). Imatinib (IM) has transient but significant activity in advanced phases of CML, which may permit early allografting for responding patients. To identify prognostic factors in allograft recipients previously treated with IM, we analyzed 449 allogeneic HSCT performed between 1999–2004 in advanced phase CML using data reported to the Center for International Blood and Marrow Transplant Research. CML patients in second chronic phase (CP2, n=184), AP (n=185), and BP (n=80) received HLA-identical sibling (27%), related (3%), or matched or mismatched unrelated donor (70%), peripheral blood (47%) or bone marrow (53%) HSCT after myeloablative (78%) or non-myeloablative (22%) conditioning. 52% in CP2, 49% in AP, and 46% in BP received IM pre-HSCT. Disease-free survival was 35–40% for CP2, 26–27% for AP and 8–11% for BP. Cumulative incidence of acute and chronic GVHD and TRM were not affected by stages of CML or pre-HSCT IM exposure. Multivariate analyses showed that conventional prognostic indicators remain the strongest determinants of transplant outcomes. In conclusion, there are no new prognostic indicators of outcomes of allogeneic HSCT for advanced phase CML in the IM era.
Imatinib; allogeneic transplantation; chronic myeloid leukemia; accelerated phase; blast phase; outcomes
A common principle of tissue regeneration is the reactivation of previously employed developmental programs [1–3]. During zebrafish heart regeneration, cardiomyocytes in the cortical layer of the ventricle induce the transcription factor gene gata4 and proliferate to restore lost muscle [4–6]. A dynamic cellular mechanism initially creates this cortical muscle in juvenile zebrafish, where a small number of internal cardiomyocytes breach the ventricular wall and expand upon its surface . Here, we find that emergent juvenile cortical cardiomyocytes induce expression of gata4 similarly as during regeneration. Clonal analysis indicates that these cardiomyocytes make biased contributions to build the ventricular wall, whereas gata4+ cardiomyocytes have little or no proliferation hierarchy during regeneration. Experimental microinjuries or conditions of rapid organismal growth stimulate production of ectopic gata4+ cortical muscle, implicating biomechanical stress in morphogenesis of this tissue and revealing clonal plasticity. Induced transgenic inhibition defined an essential role for Gata4 activity in morphogenesis of the cortical layer and the preservation of normal cardiac function in growing juveniles, and again in adults during heart regeneration. Our experiments uncover an injury-responsive program that prevents heart failure in juveniles by fortifying the ventricular wall, one that is reiterated in adults to promote regeneration after cardiac damage.
Aluminum phosphide (ALP) (celphos) is an agricultural pesticide commonly implicated in poisoning. Literature pertaining to the clinical manifestations and treatment outcome of its poisoning among children is limited.
Materials and Methods:
A retrospective chart review was conducted of the medical records of 30 children aged less than 14 years admitted to pediatric intensive care unit (PICU) of a tertiary care hospital in northern India. Demographic, clinical, and laboratory parameters were recorded. The outcome was categorized into “survivors” and “nonsurvivors.”
The Mean (SD) age of the enrolled children [19 males (63.3%)] was 8.55 (3.07) years. Among the 30 children, 14 (46.67%) were nonsurvivors and the rest 16 (53.33%) were survivors. Nonsurvivors had ingested significantly higher doses of ALP (P < 0.001), and showed higher time lag to PICU transfer (P 0.031), presence of abnormal radiological findings on chest skiagram (P = 0.007), and a higher Pediatric Risk of Mortality (PRISM) III score (P < 0.001) at admission. Use of magnesium sulfate was associated significantly with survival [odds ratio (OR) (95% CI): 0.11 (0.02-0.66); P 0.016].
The present study highlights that survival among children with ALP poisoning is predicted by dose of ALP ingestion, time lag to medical attention, and higher PRISM score at admission. Use of magnesium sulfate could be associated with better survival among them.
Magnesium sulfate; mortality; pediatric intensive care
Ruxolitinib is an oral Janus kinase (JAK) 1/JAK2 inhibitor approved in the US for the treatment of intermediate-or high-risk myelofibrosis (MF). Because thrombopoietin and erythropoietin signal through JAK2, dose-dependent cytopenias are expected with treatment. In the COMFORT-I (COntrolled Myelofibrosis study with ORal JAK inhibitor Treatment I) trial, these cytopenias were effectively managed with dose adjustments. These analyses were conducted to evaluate the relationship between ruxolitinib titrated doses and changes in platelet count and hemoglobin level as well as efficacy measures.
Patients and methods
COMFORT-I was a randomized, placebo-controlled trial in 309 patients with intermediate-2 or high-risk MF and a platelet count ≥100 × 109/L. Ruxolitinib starting doses were 15 and 20 mg twice daily (bis in die [BID]) for patients with baseline platelet counts of 100–200 × 109/L and >200 × 109/L, respectively. Percentage changes from baseline to week 24 in spleen volume and MF-related symptoms were assessed in subgroups defined by final titrated dose (average daily dose during weeks 21 to 24).
The median final titrated doses for patients starting at doses of 15 and 20 mg BID were 10 and 20 mg BID, respectively, at week 24. Most dose reductions occurred in the first 8–12 weeks of treatment and coincided with decreases in platelet count and hemoglobin level. Subsequently, platelet counts stabilized and hemoglobin levels gradually returned to near baseline levels (red blood cell transfusion rates followed a similar trend). Final titrated doses of ≥10 mg BID were associated with clinically meaningful improvements in MF-related symptoms that were comparable across doses, while marginally greater reductions in spleen volume were observed at higher doses.
This COMFORT-I analysis shows that dose-dependent cytopenias were effectively managed with ruxolitinib dose adjustments, and titrated doses of ≥10 mg BID were associated with clinically meaningful reductions in spleen volume and symptom improvement at week 24.
COMFORT-I; dose titration; JAK2 inhibitor; myelofibrosis; ruxolitinib; treatment-related cytopenias
To assess the impact of spleen status on engraftment and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil and platelet engraftment were 15 vs. 18 days and 22 vs. 24 days for the SP and NS groups, respectively (p<0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds of days +14 and +21 neutrophil and day +28 platelet engraftment were 3.26, 2.25, and 1.28 for splenectomy, and 0.56, 0.55, and 0.82 for splenomegaly groups compared to normal spleen (p<0.001), respectively. Among patients with splenomegaly, use of peripheral blood grafts improved neutrophil engraftment at day +21, and CD34+ cell dose >5.7x106/kg improved platelet engraftment at day+28. After adjusting variables by Cox regression, the incidence of graft-versus-host disease (GVHD) and overall survival were not different among groups. Splenomegaly is associated with delayed engraftment while splenectomy prior to HCT facilitates early engraftment without impact on survival.
Engraftment; splenectomy; spleen; stem cell transplantation; myeloproliferative disease
With improvements in hematopoietic cell transplantation (HCT) outcomes for severe aplastic anemia (SAA), there is a growing population of SAA survivors following HCT. However, there is a paucity of information regarding late effects that occur after HCT in SAA survivors. This study describes the malignant and non-malignant late effects in survivors with SAA following HCT. A descriptive analysis was conducted of 1,718 patients post-HCT for acquired SAA between 1995–2006 reported to the CIBMTR. The prevalence and cumulative incidences of late effects are reported for 1-year HCT survivors with SAA. Of the HCT recipients, 1,176 (68.5%) and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated donor (URD) HCT, respectively. The median age at the time of HCT was 20 years. The median interval from diagnosis to transplant was 3 months for MSD HCT and 14 months for URD HCT. The median follow-up was 70 months and 67 months for MSD and URD HCT survivors, respectively. Overall survival at 1 year, 2 years, and 5 years for the entire cohort was 76% (95% confidence interval [CI]: 74–78), 73% (95% CI: 71–75), and 70% (95% CI: 68–72). Among 1-year survivors of MSD HCT, 6% had one late effect and 1% had multiple late effects. For 1-year survivors of URD HCT, 13% had one late effect and 2% had multiple late effects. Among survivors of MSD HCT, the cumulative incidences of developing late effects were all less than 3% and did not increase over time. In contrast, for recipients of URD HCT, the cumulative incidence of developing several late effects exceeded 3% by five years: gonadal dysfunction 10.5% (95% CI: 7.3–14.3), growth disturbance 7.2% (95% CI: 4.4–10.7), avascular necrosis 6.3% (95% CI: 3.6–9.7), hypothyroidism 5.5% (95% CI: 2.8–9.0), and cataracts 5.1% (95% CI: 2.9–8.0). Our results indicated that all patients undergoing HCT for SAA remain at-risk for late effects and must be counseled about and should be monitored for late effects for the remainder of their lives.
hematopoietic cell transplant; allogeneic; survivorship; severe aplastic anemia; late effects
Bone defect has always been a challenge to treat for the orthopaedic surgeon. Fibular grafting is a popular method for bridging the gap in bone defects created by tumour excision, trauma or bone loss as sequelae to infection. Fibula is a popular substitute for this method because of its easy accessibility and minimal donor site morbidity. The present study is aimed at finding the results in paediatric population.
Material and methods
20 patients with bone defect (19 as a result of chronic osteomyelitis and one as a result of excision of a tumour) were included in the current study. The age of the patients ranged from one year to 12 years. The fibular graft was applied after freshening of bone end and fixed with K wire or plating and cancellous bone graft was also applied at both ends. The limb was immobilized in plaster till union of fibula at both ends.
The average gap was 8 cm (range 6–12 cm). Out of the twenty cases nine involved the humerus, seven in the tibia, two in radius and one each in femur and ulna. Union was achieved at both ends in 80% of the patients after the first surgery. Three out of six patients with K wire as fixation device failed and one out of fourteen patients with plate as fixation device ended in non-union. Union was achieved in these patients after revision surgery. One patient had stress fracture at distal end of the plate after weight bearing. Union occurred in this patient after plaster immobilization. Range of motion at distal and proximal joint was comparable to normal side. Superficial infection was seen in two patients and they responded to antibiotics.
Non-vascularised fibular grafting is a good option for bone defects in paediatric population provide adequate fixation and immobilization has been done.
Level of evidence
Level IV (Therapeutic).
Bone defect; Non-vascularised fibular grafting; K wire; Osteomyelitis
The HLA class II DRB1 antigen DR15 (common alleles *1501, *1502) is an important marker in the pathobiology of severe aplastic anemia (SAA). We studied 1204 recipients of HLA-matched sibling bone marrow transplantation for SAA to determine whether HLA-DR15 status (as determined by allele-level typing) affected hematopoietic recovery, graft-versus-host disease (GvHD) or overall survival. In multivariate analysis, secondary graft failure rate at 2-years was lower in patients who are HLA-DR15+ (hazard ratio 0.46, p=0.01). However, neutrophil recovery at day-28, platelet recovery at day-100, acute GvHD, chronic GvHD and overall mortality were independent of DR15 status. The 5-year probabilities of overall survival, after adjusting for age, race, performance score, transplant-conditioning regimen and year of transplantation, were 78% and 81% for patients who are HLA-DR15+ and HLA-DR15-, respectively (p=0.35). In conclusion, DR15 status is associated with secondary graft failure after HLA-matched sibling bone marrow transplantation for SAA but has no significant impact on survival.
DR15; SAA; GvHD; Survival; Graft Failure
Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splenectomy. Most patients (69%for ET and 67%for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus- host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47%and 71%/48% for ET and PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS.
Transplantation; PV; ET
Wegener's granulomatosis (WG) is a systemic necrotizing vasculitis that affects the small blood vessels. It mainly affects the upper and lower respiratory tract and kidneys. Central nervous system (CNS) involvement is rare, and has been reported only in about 8% of cases during the course of illness. Initial presentation with neurologic affection, particularly chronic hypertrophic meningitis is very unusual. We report the case of a 34 year old male who presented with chronic hypertrophic meningitis and multiple cranial nerve involvement as the initial manifestation, without respiratory and renal symptoms. This case highlights the difficulties in diagnosing a rare disease with rarer presentation, and at the same time illustrates that Wegener's granulomatosis should be considered in the differential diagnosis of chronic meningitis.
Chronic meningitis; cranial neuropathies; Wegener's granulomatosis
Hashimoto encephalopathy remains a Rubik's cube for the present generation of clinical research. Myriad presentations have been noted, and observations recorded in few subgroups of patients have gone on only to be trashed by a second group of patients with a completely different clinical profile. Steroids have been traditionally held to be the treatment for this condition, but long-term side effects associated with it limits its use. Although multiple drugs have been tried, yet there exists no data for their long-term efficacy in maintaining remission. No radiological findings have been consistently associated with this condition. We report the use of azathioprine in maintaining long-term remission in one such patient with Hashimoto encephalopathy and the presence of lactate peak in magnetic resonance spectroscopy of the patient, which showed dramatic regression with institution of immunosuppression.
Anti-thyreoperoxidase; azathioprine; encephalopathy; lactate peak; methylprednisolone; MRI-spectroscopy
Immediately after the annual scientific meeting of the American Society of Hematology (ASH), a select group of clinical and laboratory investigators in myeloproliferative neoplasms (MPN) is summoned to a post-ASH conference on chronic myeloid leukemia and the BCR-ABL1-negative MPN. The 6th such meeting occurred on 13th–14th December 2011, in La Jolla, California, USA, under the direction of its founder, Dr. Tariq Mughal. The current document is the first of two reports on this post-ASH event and summarizes the most recent preclinical and clinical advances in polycythemia vera, essential thrombocythemia and primary myelofibrosis.
ASXL1; EZH2; JAK2; myelofibrosis; myeloproliferative neoplasms; TET2; thrombocythemia
The scaphoid is the common carpal bone to be fractured. Proper clinical and radiological evaluation is required to establish it's diagnosis. The management of acute fractures includes conservative treatment with cast in minimally displaced to open reduction and internal fixation in case of displaced ones. The established nonunion requires open reduction, bone grafting and internal fixation.
Scaphoid fractures; Percutaneous fixation; Herbert–Whipple screw; Vascularized bone graft
Cytogenetics play a major role in determining the prognosis of patients with AML. However, the existing cytogenetics classifications were developed on chemotherapy-treated patients and may not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the CIBMTR who underwent HCT for AML in first or second CR between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival (OS). We then defined a new schema specifically applicable to HCT patients using this patient cohort. Under this CIBMTR schema, inv(16) is favorable, complex karyotype (4+ abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5y OS 64%, 18%, and 50%, respectively, p=0.0001). This schema stratified patients into 3 groups with similar non-relapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applied to patients regardless of their disease status (CR1 or CR2), donor type (MRD or URD), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials.
AML; cytogenetics; stem cell transplantation