Louis Letendre

Outcome of Recipients of Bone Marrow Transplants Who Require Intensive-Care Unit Support

To determine the outcome and prognostic factors associated with bone marrow transplantation (BMT), we reviewed the clinical course of 35 adult recipients of such a transplant who were admitted to our intensive-care unit (ICU). This constituted 24% of patients who underwent BMT for treatment of hematologic disorders during the study period. The reasons for admission to the ICU were postsurgical care in 5, respiratory failure in 25, shock in 4, and renal failure in 1. The in-hospital mortality was 20% for the postsurgical patients and 87% for the others. None of the postsurgical patients required mechanical ventilation, whereas 90% of the others did, and the associated mortality was 93%. Infection was the cause of the respiratory failure in all but 3 of the 25 patients and was associated with 95% mortality. Complications that involved multiple organs increased the mortality to 100%. No significant differences were found in age, sex, type of BMT, serologic tests for cytomegalovirus, history of graft-versus-host disease, conditioning regimen for BMT, and duration of stay in the ICU and the hospital between survivors and nonsurvivors. The APACHE II (acute physiology and chronic health evaluation) prognostic scoring system underestimated mortality and had no correlation with the duration of stay in the ICU or the hospital. Vasopressors, total parenteral nutrition, and transfusion of blood components in the ICU had no influence on the outcome. Open-lung biopsy was helpful in making specific diagnoses, and pulmonary artery catheters were used in most patients to guide therapy but did not improve survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia

Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkins lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/μl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12–75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 ⩾500 cells/μl compared with 22 patients with ALC <500 cells/μl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC ⩾500 cells/μl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.

Prognostic Factors and Outcomes of Adults With Hemophagocytic Lymphohistiocytosis

OBJECTIVE To describe the prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system. PATIENTS AND METHODS The study population consisted of a consecutive cohort of adult (age ≥18 years) patients treated at Mayo Clinic in Rochester, Minnesota, from January 1, 1996, through December 31, 2011, in whom a diagnosis of HLH was suspected and subsequently confirmed by retrospective review using the HLH-04 diagnostic criteria. RESULTS Of 250 adult patients suspected of having HLH, 62 met the HLH-04 diagnostic criteria and were included in the final analysis. The median age was 49 years (range, 18-87 years), and 42 (68%) were male. The underlying cause of HLH was malignant tumor in 32 patients (52%), infection in 21 patients (34%), autoimmune disorder in 5 patients (8%), and idiopathic disease in 4 patients (6%). After a median follow-up of 42 months, 41 patients (66%) had died. The median overall survival of the entire cohort was 2.1 months. The median overall survival of patients with tumor-associated HLH was 1.4 months compared with 22.8 months for patients with non-tumor-associated HLH (P=.01). The presence of a malignant tumor and hypoalbuminemia were significant predictors of inferior survival on multivariate analysis. CONCLUSION In this large series of adults with secondary HLH treated at a single tertiary care center, patients with low serum albumin levels and tumor-associated HLH had a markedly worse survival. Hemophagocytic lymphohistiocytosis remains elusive and challenging to clinicians who must maintain a high index of suspicion. The recent discovery of several novel diagnostic and therapeutic modalities may improve outcomes of adult patients with HLH.

Nilotinib treatment-associated peripheral artery disease and sudden death: Yet another reason to stick to imatinib as front-line therapy for chronic myelogenous leukemia†

Aichberger and colleagues recently described an association between nilotinib therapy for chronic myelogenous leukemia (CML) and adverse vascular events, which occurred in eight (~33%) of their 24 CML patients treated with nilotinib: severe peripheral artery disease (PAD; n = 3), less severe PAD (n = 1), sudden death (n = 1), myocardial infarction (n = 1), spinal infarction (n = 1), and subdural hematoma (n = 1) [1]. We were intrigued by these observations because of similar events that occurred in two of our patients receiving nilotinib therapy. A female patient developed severe and unrelenting PAD and coronary artery disease (CAD) after ~3 years of treatment with nilotinib and the second patient died suddenly after receiving nilotinib therapy for 3 weeks. None of the two patients had history of cardiovascular disease, tobacco use, or diabetes mellitus. These observations are troubling and question the prudence of rushing to replace imatinib with nilotinib, for front-line therapy in CML.

Acute Leukemia during Pregnancy: A Single Institutional Experience with 17 Cases

We reviewed the medical records of 17 consecutive patients with concomitant acute leukemia and pregnancy seen at our institution over a 37-year period. Fifteen cases each were either newly diagnosed or classified as acute myeloid leukemia (AML). Seven diagnoses (41%) occurred in the first, 7 (41%) in the second, and 3 (18%) in the third trimester. In general, nine patients received chemotherapy while pregnant—eight in the second trimester and one in the third. The overall complete remission rate among the 13 patients with newly diagnosed AML was 69%, compared with 86% in those who were pregnant during chemotherapy. Long-term survival was documented in five of the nine complete responders. Three of four patients who elected to delay treatment until after delivery died within days of starting chemotherapy. Unintentional fetal loss occurred in four patients (29%), including two without exposure to chemotherapy. There were no instances of congenital malformation. The results from the current study confirm that pregnancy per se may not affect the outcome of chemotherapy in AML. In addition, it is suggested that treatment delays may compromise maternal outcome without improving pregnancy outcome.

Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia

Prognosis in chronic myelomonocytic leukemia (CMML) is unfavorable and the optimal therapy remains uncertain. Currently, allogeneic stem cell transplantation is the only known curative therapeutic option. However, the data available are limited and restricted to small retrospective series. There is even less information on the use of donor lymphocyte infusions (DLI) for this disease. We reviewed our experience of allogeneic stem cell transplantation and DLI for adults with CMML. Seventeen consecutive adults underwent allogeneic stem cell transplantation from related (n=14) or unrelated (n=3) donors. Median age was 50 years (range 26–60). Seven patients (41%) demonstrated relapse or persistent disease at a median of 6 months (range 3–55.5). Five patients underwent DLI for morphologic relapse and one for mixed donor chimerism. Two patients achieved durable complete remissions of 15 months each. The overall transplant-related mortality was 41% (n=7). With a median follow-up of 34.5 months, three patients (18%) currently remain alive and in continuous CR. The current study demonstrates a graft-versus-leukemia effect in CMML, both for allogeneic stem cell transplantation and for DLI. Nevertheless, consistent with reported experience of others, overall outcomes remain less than optimal and unpredictable.

Thromboembolism in Adults with Acute Lymphoblastic Leukemia During Induction with L-Asparaginase-containing Multi-agent Regimens: Incidence, Risk Factors, and Possible Role of Antithrombin

Thromboembolism (TE) is a known complication of L-asparaginase (ASP) therapy of acute lymphoblastic leukemia (ALL), possibly attributable to reduced synthesis of natural anticoagulants, in particular antithrombin (AT). This retrospective single institution study was performed to determine the TE incidence among adults undergoing induction with contemporary, ASP-containing regimens. Ten of 54 (18.5%) consecutive adults developed symptomatic, objectively confirmed TE, at a median of 5.5 days after the first ASP dose. These were notable for CNS and upper extremity localization, varied significantly according to ALL immunophenotype (precursor B: 11% vs. T cell: 33%), without apparent effect of schedule or total dose of ASP. Median baseline AT level was 94% and fell to a nadir of 47% (P < 0.0001) during ASP therapy. Prophylactic AT had been given to 17 during ASP therapy. None of these developed TE vs. 10/37 (27%) without replacement (P = 0.021). These observations merit further study to gain insight into disease and/or therapy-specific pathogenesis of TE in this population and call for the prospective evaluation of appropriate prophylactic interventions.

Deletions of chromosome 13 in malignant hematologic disorders

Thirteen patients with a hematologic disorder and an interstitial deletion of part of a chromosome #13 were evaluated to determine if any specific clinical manifestations are associated with these cytogenetic anomalies. Our results suggest that these anomalies occur in approximately 1.7% of patients with a chromosomally abnormal clone and a hematologic disorder. They may occur as the sole chromosome anomaly (8 of our patients) or with other abnormalities (5 of our patients). The breakpoints are not always the same, but band 13q14 always seems to be lost. At the time of chromosome analysis, 5 patients had a history of myelofibrosis or agnogenic myeloid metaplasia, 2 had acute nonlymphocytic leukemia, 2 had a myelodysplastic syndrome, one had polycythemia vera, one had sideroblastic anemia, one had acute lymphocytic leukemia, and one had an undifferentiated myeloproliferative disorder.

Cancer-associated microangiopathic hemolytic anemia with thrombocytopenia: an important diagnostic consideration

Background:  Early initiation of plasma exchange (PE) allows more than 80% of patients with idiopathic thrombotic thrombocytopenic purpura (TTP), most commonly because of severe ADAMTS13 deficiency, to achieve remission and mandates urgency in diagnosis and therapy. Metastatic cancer may present with a microangiopathic hemolytic anemia with thrombocytopenia that is clinically similar to TTP but does not respond to PE. ADAMTS13 activity can be diagnostic but usually not immediately available. Recognition of cancer‐associated microangiopathic hemolytic anemia with thrombocytopenia (CA‐MHA) is paramount to avoid inappropriate PE therapy and delays in cancer‐specific chemotherapy.

Evaluation of a somatostatin analog in the treatment of lymphoproliferative disorders: results of a phase II North Central Cancer Treatment Group trial.

PURPOSE Malignant cells from non-Hodgkins lymphomas (NHL) have been shown to express the somatostatin receptor on their cell surface and most NHL are visible on somatostatin radioscintigraphy scans. This provided the rationale to conduct a phase II trial of a somatostatin analog in patients with B- and T-cell lymphoproliferative disorders. PATIENTS AND METHODS Sixty-one patients with measurable or assessable lymphoproliferative disorders (31 stage III or IV low-grade NHL; 21 chronic lymphocytic leukemia [CLL]; and nine cutaneous T-cell NHL [CTCL]) were enrolled. Patients were treated with somatostatin 150 micrograms subcutaneously (SQ) every 8 hours for 1 month. Patients with stable or responding disease received 2 additional months of therapy; those who responded after 3 months were treated for an additional > or = 3 months. RESULTS Sixty patients were assessable for toxicity and 56 for response. There were no complete remissions. In the low-grade NHL group, 36% (10 of 28 patients; 95% confidence interval [CI], 19% to 56%) had a partial remission. Forty-four percent (four of nine; 95% CI, 14% to 79%) of patients with CTCL had a partial response. No patients with CLL had a partial remission. Among 45 patients with stable disease or a partial remission, the mean time to progression (TTP) was 10.9 months (median, 6.2; range, 1.6 to 48.5). The drug was well tolerated, with the most common side effects being diarrhea and hyperglycemia. CONCLUSION Somatostatin at a dose of 150 micrograms every 8 hours is well tolerated and has activity in low-grade NHL.