Objective
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition associated with multiple organ dysfunction. We sought to describe ICU management and outcomes in HLH patients ...meeting HLH-2004 criteria and to identify determinants of mortality.
Design
Retrospective study between January 1998 and January 2009.
Setting
Medical ICU of a teaching hospital.
Patients
Among the 72 patients fulfilling the HLH-2004 criteria, we report the 56 patients with complete follow-up and no missing data.
Interventions
None.
Measurements and main results
Clinical and laboratory data were abstracted from the medical records. Median SOFA score at admission was 6.5 (IQR, 4–8). At ICU admission, the number of HLH-2004 criteria was 6 (5–7). Sixty-six precipitating factors were found in 52 patients and consisted of 43 tumoral causes (8 Castleman’s diseases, 18 B cell lymphoma and 17 various malignancies), 13 non-viral infections and 10 viral infections. Underlying immune deficiency was present in 38 (67.8%) patients. Etoposide was used in 45 patients, corticosteroids in 31 and intravenous immunoglobulins in 3. Mechanical ventilation was required in 32 patients, vasoactive agents in 30 and renal replacement therapy in 19. Hospital mortality was 29/56 patients. By multivariate analysis, factors associated with increased hospital death were shock at ICU admission OR, 4.33; 95% confidence interval (95% CI), 1.11–16.90;
P
= 0.03 and platelet count <30 g/l (OR, 4.75; 95% CI, 1.20–18.81;
P
= 0.02). B cell lymphoma odds ratio (OR), 0.17; 95% CI, 0.04–0.80;
P
= 0.02 and Castleman’s disease (OR, 0.11; 95% CI, 0.02–0.90;
P
= 0.04) were associated with increased hospital survival.
Conclusions
Aggressive supportive care combined with specific treatment of the precipitating factor can produce meaningful survival in patients with HLH responsible for multiple organ failures. Survival is highest in patients with HLH related to Castleman’s disease or B cell lymphoma.
Abstract Purpose Acute promyelocytic leukaemia (APL) therapy with all-trans retinoic acid and chemotherapy is associated with a high cure rate in clinical trials. As some patients are not enrolled in ...these trials due to early severe events, these results might be overestimated. To address this issue, we reviewed all APL patients referred to the Hospital Saint-Louis within the 2000–2010 period, with a special focus on inclusion in recruiting trials. Patients and methods One hundred patients (including eight children) with newly diagnosed APL were admitted during this period, which covered two consecutive APL trials conducted by the French-Belgian-Swiss APL group. Results The rate of patients not enrolled within recruiting trials was 29%. The main reason for non-inclusion was protocol ineligibility related to disease severity at diagnosis. Non-enrolled patients more frequently had white blood cell count (WBC) ⩾ 50 × 109 /L (31% versus 8%; p = .01), platelet count < 40 × 109 /L (97% versus 65%; p = .001) and microgranular variant APL (38% versus 11%; p = .004) and were more frequently admitted in intensive care unit during induction (41% versus 24%; p = .094). Early mortality rate was higher in non-enrolled patients (21% versus 3%; p = .007), translating into a lower complete remission rate (79% versus 96%; p = .007) and lower event-free survival (65% versus 84% at 5 years; p = .05), while disease-free survival was similar in both non-enrolled and enrolled patient groups (81% versus 88% at 5 years; p = .68). Conclusion Initial APL severity leads to a significant proportion of patients non-registered within clinical trials, which may underestimate the real early mortality, which remained nonetheless less than 10% in this study.
Purpose
Multicentric Castleman disease (MCD) is a distinct lymphoproliferative disorder characterized by inflammatory symptoms, lymphadenopathy, splenomegaly, and cytopenia. Kaposi's ...sarcoma‐associated herpesvirus (KSHV), also called human herpesvirus‐8 (HHV‐8), is the cause of virtually all cases of MCD occurring in patients with HIV infection. MCD lesions characteristically contain HHV‐8‐infected polyclonal IgMλ plasmablasts. A high frequency of HHV‐8‐related non‐Hodgkin lymphoma has been reported in these patients.
Patients and methods
We now report on three patients who presented with severe symptoms of MCD, extreme splenomegaly, and rapid expansion of B‐cell lymphocytosis (44–81%) attributable to circulating HHV‐8 positive plasmablasts.
Results
The circulating plasmablastic cells shared the phenotype (IgMλ, CD19+, CD20− CD138−) of HHV‐8‐infected cells from MCD lesions, mimicking the leukemic phase of large B‐cell lymphoma occurring in HHV‐8‐related MCD. These patients displayed a very high HHV‐8 viral load in blood (>7 logs HHV‐8 DNA copies/ml) and high levels of serum vIL‐6, the viral homolog of human interleukin 6. Serum IL‐6 and IL‐10 were also abnormally elevated. HHV‐8‐infected cells were demonstrated by immunoglobulin gene rearrangement analysis, to be polyclonal and likely represent an expansion of HHV‐8‐infected cells similar to those found in MCD lesions.
Conclusion
Thus, the spectrum of HHV‐8‐related plasmablastic lymphoproliferative disorders in patients with HIV infection is expanded to include HHV‐8+ polyclonal IgMλ B‐cell lymphocytosis. At onset, this lymphoproliferative disorder may mimic plasmablastic leukemia/lymphoma. Recognizing this unusual complication may have important implications in treatment decision avoiding unnecessary toxicity to the patients.
To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS.
...Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres.
Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan-Meier method.
Fifty-eight HIV-1-infected patients were diagnosed with RHS certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23-85) years, men 76%. At time of RHS, the median duration of HIV infection was 4 (0-22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2-387)/microl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/microl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68).
In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era.
The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and ...2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL real-time quantitative polymerase chain reaction (RQ-PCR) negativity rates were 96% and 29%, respectively. All of the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, the estimated cumulative incidence of relapse, disease-free survival, and overall survival were 30%, 51%, and 65%, respectively. These 3 end points compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context.
In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) ...or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count.
We describe a 35-year-old woman who presented with proteinuria and microscopic haematuria. Blood tests revealed a low C3 complement level, with no evidence of cryoglobulin. Renal biopsy showed a Type ...1 membranoproliferative glomerulonephritis (MPGN) with isolated C3 deposits on immunofluorescence study. Bone marrow aspirate, done for monocytopenia, was consistent with a diagnosis of hairy cell leukaemia (HCL). Both haematological and nephrological diseases completely responded to treatment with cladribine, strongly suggesting that the renal disease was a paraneoplastic syndrome. To our knowledge, this is the first report of a non-cryoglobulinaemic MPGN associated to HCL.
Abstract
Purpose
Multicentric Castleman disease (
MCD
) is a distinct lymphoproliferative disorder characterized by inflammatory symptoms, lymphadenopathy, splenomegaly, and cytopenia. Kaposi's ...sarcoma‐associated herpesvirus (
KSHV
), also called human herpesvirus‐8 (
HHV‐8
), is the cause of virtually all cases of
MCD
occurring in patients with
HIV
infection.
MCD
lesions characteristically contain
HHV
‐8‐infected polyclonal IgMλ plasmablasts. A high frequency of
HHV
‐8‐related non‐Hodgkin lymphoma has been reported in these patients.
Patients and methods
We now report on three patients who presented with severe symptoms of
MCD
, extreme splenomegaly, and rapid expansion of
B
‐cell lymphocytosis (44–81%) attributable to circulating
HHV
‐8 positive plasmablasts.
Results
The circulating plasmablastic cells shared the phenotype (IgMλ,
CD
19+,
CD
20−
CD
138−) of
HHV
‐8‐infected cells from
MCD
lesions, mimicking the leukemic phase of large B‐cell lymphoma occurring in
HHV
‐8‐related
MCD
. These patients displayed a very high
HHV
‐8 viral load in blood (>7 logs
HHV
‐8
DNA
copies/ml) and high levels of serum
vIL
‐6, the viral homolog of human interleukin 6. Serum
IL
‐6 and
IL
‐10 were also abnormally elevated.
HHV
‐8‐infected cells were demonstrated by immunoglobulin gene rearrangement analysis, to be polyclonal and likely represent an expansion of
HHV
‐8‐infected cells similar to those found in
MCD
lesions.
Conclusion
Thus, the spectrum of
HHV
‐8‐related plasmablastic lymphoproliferative disorders in patients with
HIV
infection is expanded to include
HHV
‐8+ polyclonal IgMλ
B
‐cell lymphocytosis. At onset, this lymphoproliferative disorder may mimic plasmablastic leukemia/lymphoma. Recognizing this unusual complication may have important implications in treatment decision avoiding unnecessary toxicity to the patients.
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