Immune Thrombocytopenia in Type I Gaucher Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3200-3200 ◽  
Author(s):  
Hanna Rosenbaum ◽  
Tina Napso ◽  
Lilach Bonstein
Keyword(s):  
Bone Marrow ◽  
Gaucher Disease ◽  
Immune Modulation ◽  
Hematological Parameters ◽  
Autoimmune Disorder ◽  
Type I ◽  
Bleeding Tendency ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Enzyme Replacement

Abstract Backgound: Type I Gaucher disease (GD) the non-neuronopathic form is characterized by hepatosplenomegaly, pancytopenia and skeletal complications due to the accumulation of glucocerebroside in macrophages. Thrombocytopenia is usually related to hypersplenism and/or infiltration of bone marrow by the lipid-laden macrophages namely Gaucher cells. Enzyme replacement therapy (ERT) restores the hemoglobin and platelet count in treated GD patients within 12–24 months of treatment. In GD patients, including ERT treated, with persistent low platelet counts other ethiological factors should be considered. Goals: To determine the etiology of persistent thrombocytopenia in Type I GD patients and to evaluate their clinical course and hematological parameters. Methods: Flow cytometric technique was used to detect platelet-surface associated IgG/M (PSIgG/M) in a cohort of 24 Type I GD patients followed at the Gaucher clinic in Haifa, Israel. The evaluated hematological parameters of the thrombocytopenic GD patients include: bleeding phenomena, concurrence of autoimmune phenomena, hematological malignancies and bone marrow findings. Results: Twenty four Type I GD patients, 15 females and 9 males with an age range of 35 to 80 years (median 53 years) were included in the study. Seventeen of the evaluated 24 patients were thrombocytopenic with platelet counts less than <100×109/l and 7/24 were in the normal range. Bone marrow aspirate was performed in 16 of the 17 thrombocytopenic patients and showed normal or hyperplasic megakariopoiesis together with Gaucher cells infiltrates. Six of the 17 thrombocytopenic patients received ERT for at least 24 months with no effect on the low platelet counts. Elevated platelet surface IgG was detected in 16/17(94%) of GD patients with thrombocytopenia and in only 1/7 (14%) of non thrombocytopenic patients (p<0.0001). In 6/17 of the thrombocytopenic patients, surface IgM (PSIgM) was found, in addition to the PSIgG. Those six patients are known with monoclonal IgM (concomitant Waldenstrom macroglobulinemia), markedly elevated polyclonal IgM levels, or lupus like autoimmune disorder which may have been responsible for the positive PSIgM. Only three thrombocytopenic patients with platelet counts less than 40×109/l had bleeding tendency (mainly purpura) with no response to steroid treatment (two of them were also resistant to ERT concerning their thrombocytopenia). Conclusions: Thrombocytopenia in Type I GD is related to either infiltration of bone marrow compromising megakariopoiesis or hypersplenism, but immune factors should also be considered. Despite the lack of response to steroids, the observed megakaryocytic hyperplasia in Gaucher infiltrated marrows, the failure to respond to ERT, and the presence of platelet surface antibodies in the thrombocytopenic patients, strongly implicate autoimmune etiology. The present study demonstrates that surface platelet antibodies may play a role in refractory thrombocytopenic GD patients. Since the role of splenectomy is controversial in GD, immune modulation approach should be considered.

Novel Management of Immune Thrombocytopenia in Gaucher Disease Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5006-5006
Author(s):  
Hanna Rosenbaum
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Avascular Necrosis ◽  
Gaucher Disease ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Type I ◽  
Platelet Counts ◽  
Skeletal Complications

Abstract Type I Gaucher disease (GD) the is characterized by hepatosplenomegaly, pancytopenia and skeletal complications due to the accumulation of glucocerebroside in macrophages. Thrombocytopenia is usually related to hypersplenism and infiltration of bone marrow by lipid-laden macrophages namely Gaucher cells. Enzyme replacement therapy (ERT) restores the hemoglobin and platelet count in GD patients. In GD ERT treated patients, manifesting persistent low platelet counts, immune thrombocytopenia (ITP) should be considered.Treatment of GD with concomitant ITP is a challenge. Splenectomy may worsen bone manifestations in GD patients and is controversial. Steroids should be used with caution because of possible induction of osteopenia and joints avascular necrosis. Thrombopoietin receptor analogues (TPO-RA) are therapeutic option in GD patients with ITP. Beneficial use of TPO-RA is reported in 2 cases. Patient 1: 39 YO male with new onset of purpura and low platelet count failed treatment with 1 mg/kg of Prednisone. Bone marrow biopsy (BM) showed Gaucher cells infiltration, numerous atypical megakaryocytes, normal erythropoiesis and myelopoiesis with no fibrosis. Low level of ß-glucocerebrosidase activity with compound heterozygosity for 84GG /R495H mutations, established the diagnosis of Type I GD. Low C4 and detection of IgG platelet antibodies added to the diagnosis of concomitant immune thrombocytopenia. ERT with taliglucerase alfa (ElelysoTM) 60 Units/kg/month was given with Prednisone for six weeks. Occurrence of retinal bleeding and purpura, with decrease of platelet count necessitated addition of high-dose IVIG with no response regarding platelet counts. Splenectomy was not considered due to known bony complication risk in splenectomised GD patients. Rituximab was given to prevent wet purpura recurrence with short response regarding platelet count. Romiplostim was initiated raising platelet count from 29,000/µL to 60,000/µL after 3 wks. and to 90,000/µL after 8 wks. enabling corticosteroids withdrawal. Same dose Romiplostim is maintained for the last 30 months with platelet counts of 90,000 - 110,000/µL with no bleeding events. Repeated BMB showed no increase in collagen fibrosis. Patient 2: 63 YO female patient diagnosed with Gaucher at age 33 with a history of purpura, ecchymosis, and occasional vaginal bleeding episodes. At age 53 the platelet count dropped to < 20,000/µL with presence of Anti Platelets Ab (IgG). BMB revealed megakaryocytic hyperplasia with atypical forms, focal infiltration by Gaucher cells and no fibrosis. Combined therapy by ERT (Imiglucerase® followed by Velaglucerase Alfa®), Prednisone (1mg/kg/d for 2 months) and one course of IVIG yielded no increase in platelet count. The patient refused Rituximab®. Romiplostim was initiated increasing platelet count to100,000/µL maintained throughout a year of follow up. Repeated BMB showed slight increase of fibrosis and marked hyperplasia of atypical megakaryocytes. Discussion: Thrombocytopenia is often present in GD and may be severe in approximately 15% of the patients. Persistent cytopenias may be caused by other underlying pathologies such as autoimmune disorders and are important to be recognized and addressed. Before ERT era GD patients with hypersplenism and severe cytopenia were splenectomised. Risks of splenectomy include serious bacterial infection and vascular complications limiting its use in chronic refractory ITP. Splenectomy is avoided in Gaucher patients, due to risk of exacerbating skeletal complications (bone infarcts, avascular necrosis). Stable bone marrow results regarding fibrosis in our patients are consistent with data from a recent 2-year follow-up of 100 ITP patients receiving Romiplostim treatment with no evidence of BM fibrosis. Conclusion: In patients with type I Gaucher disease and concomitant ITP, adjunctive treatment with Romiplostim was successful in maintaining haemostatic platelet counts with no adverse effects. Traditional treatment regimens of corticosteroids and splenectomy should be used with caution or avoided in GD patients due to possible aggravation of Gaucher skeletal disease and the risk of osteopenia and avascular necrosis resulting in increased morbidity in this cohort of patients. Use of TPO-RA should be considered in GD patients with ITP. Disclosures Off Label Use: Romiplostim in gaucher patients.

RESPONSE TO ENZYME REPLACEMENT THERAPY IN PATIENTS WITH GAUCHER DISEASE TYPE I

2019 ◽  
Vol 22 (06) ◽  
pp. 103-117
Author(s):  
Mays Al-Tai ◽  
Deia Al-Asady ◽  
Rula Hamid
Keyword(s):  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Gaucher Disease ◽  
Disease Type ◽  
Type I ◽  
Enzyme Replacement

Phase I/II, Nine Month Study Results of Enzyme Replacement Therapy with Gene Activated Human Glucocerebrosidase (GA-GCB) in Patients with Type I Gaucher Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3882-3882
Author(s):  
Ari Zimran ◽  
Candida Fratazzi ◽  
Robert Mensah ◽  
Deborah Elstein
Keyword(s):  
Enzyme Replacement Therapy ◽  
Phase I ◽  
Replacement Therapy ◽  
Dose Escalation ◽  
Gaucher Disease ◽  
Clinical Activity ◽  
Target Cells ◽  
Type I ◽  
Enzyme Replacement ◽  
Study Results

Abstract AIMS: Evaluation of safety and clinical activity of Gene-Activated ® human glucocerebrosidase (GA-GCB) as a new intravenous enzyme replacement therapy (ERT) for patients with type I Gaucher disease participating in a 9 month, open-label Phase I/II clinical study. BACKGROUND: GA-GCB is human glucocerebrosidase (GCB) produced in a well-characterized, continuous human cell line using proprietary gene activation technology. GA-GCB has an identical amino acid sequence to the naturally occurring human enzyme and contains terminal mannose residues that target the enzyme to macrophages, the primary target cells in Gaucher disease. Nine month study results of GA-GCB treatment will be presented. METHODS: Twelve adult patients (7 females /5 males) with type I Gaucher disease with clinically significant anemia, thrombocytopenia, hepatomegaly and/or splenomegaly, were enrolled in a 9 month Phase I/II clinical trial. Patients received GA-GCB every other week for a total of 40 weeks (20 infusions). A staggered dose escalation of GA-GCB was performed in the first 3 patients: these patients received 15 U/kg at the first infusion, 30 U/kg at the second infusion, and then 60 U/kg IV every other week for a total of 20 IV infusions. The remaining 9 patients received 60 U/kg beginning with their first dose. Anti-GA-GCB antibodies were tested in all patients during the 9 months of treatment. All patients were routinely evaluated for hemoglobin, platelets, liver and spleen volumes, infusion reactions and adverse events. In addition, serum samples were analyzed for disease biomarkers: chitotriosidase and CCL18. RESULTS: Eleven of the 12 patients who were enrolled in the trial have been treated for nine months. One patient withdrew consent after three injections for reasons not related to treatment. Dose escalation from 15 U/kg to 60 U/kg was well tolerated in the first three patients. The remaining patients received 60 U/kg every other week throughout the course of the study. Anti-GA-GCB antibody test results were negative for all patients. Mean hemoglobin and platelet values, below the normal range at baseline, improved after 9 months of GA-GCB treatment to levels consistent with the therapeutic goals for ERT in Gaucher disease (Seminars in Hematology 2004). Analysis of the liver and spleen volumes decreased following 9 months of treatment. In addition, serum chitotriosidase and CCL18 levels decreased over the 9 months of GA-GCB treatment. CONCLUSION: ERT with GA-GCB was well tolerated and demonstrated clinical activity in well-established clinical markers in patients with type 1 Gaucher disease when administered IV every other week at 60 U/kg over 9 months. Results suggest that GA-GCB holds promise as a new therapeutic option for ERT in Gaucher disease.

Danazol Increases ADAMTS13 Activity and Reduces Requirement for Therapeutic Exchange Plasmapheresis (TEP) and Plasma Infusion in Patients with TTP.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1057-1057
Author(s):  
Eugene Ahn ◽  
Wenche Jy ◽  
Loreta Bidot ◽  
John Byrnes ◽  
Joaquin Jimenez ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Autoimmune Disorder ◽  
Myeloproliferative Disorders ◽  
Adamts13 Activity ◽  
Central Lines ◽  
Platelet Counts ◽  
Group A ◽  
Hospital Stays ◽  
The Mean ◽  
Group B

Abstract INTRODUCTION: Therapeutic plasma exchange with infusion of FFP (TPE/FFP) is a standard therapy for TTP. However TPE requires insertion of central lines and is associated with increased morbidity such as line-related infections and sepsis. Danazol has two relevant properties: immune modulation and enzyme induction. The former was exploited in autoimmune diseases such as ITP and the latter in disorders of enzyme deficiencies such as hereditary angioneurotic edema. TTP is an autoimmune disorder with deficiency of the enzyme, ADAMTS13. We investigated danazol therapy in patients with TTP and measured ADAMTS13 activities prior to and post danazol. METHODS: We studied 7 patients (pts) with diagnosis of TTP, and 10 non-TTP pts (4 ITP, 2 thrombocytopenias of other cause, 2 autoimmune hemolytic anemia, 2 lympho- or myeloproliferative disorders). Both TTP and non-TTP patients were treated with danazol. All 7 TTP patients were female with mean age of 42. Four of the TTP patients (Group A) failed or had complications with TPE/FFP, requiring over 2 wks of hospitalization prior to starting danazol. The new regimen includes (1) administration of danazol at 200 mg 2–4 times daily, (2) removal of central lines and discontinuation of TPE when platelet counts stabilized, (3) infusion of FFP through peripheral vein. While monitoring platelet counts and LDH, FFP infusion was gradually tapered and stopped and danazol was continued for an additional 8–20 wks. In the remaining pts with TTP (Group B), danazol was started on admission along with TPE in two pts and FFP alone in one. ADAMTS13 was assayed by the FRETS-vWF73 method [Brit J Haem2005; 129:93] before and after 2–5 wks of danazol. Parameters evaluated were clinical and laboratory improvement, complications, requirement for TPE and FFP, and levels of ADAMTS13 activity. RESULTS: All 4 pts in Group A, who failed or had complications with TPE/FFP, responded well to the regimen, requiring fewer TPE and FFP infusions. The mean number of TPE was reduced by 88% post-danazol and mean number of FFP reduced by 79%. Their hospital stays were shorter. The 3 pts (Group B) who received danazol on admission also responded well. Patient B#1, with 20 yr history of TTP and numerous recurrences, required 1–2 weeks of hospitalizations with the new regimen, compared to 3–8 wks in her previous admissions. Patient B#3 who had FFP infusion alone had an excellent response but danazol had to be stopped because of abnormal liver function; she then relapsed necessitating TPE/FFP. ADAMTS13 activities were measured in 5 TTP pts: mean activity rose from 25.2% pre-danazol to 80.2% post (p=0.007). In the 10 non-TTP pts, the mean activity increased from 61.1% to 75.0% (p=0.03) pre-/post-danazol. CONCLUSION. Danazol with FFP infusion was effective in all TTP pts. Danazol significantly reduced requirement of TPE and infusion of FFP and increased ADAMTS13 activity in both TTP and non-TTP patients. Use of danazol with FFP infusion through peripheral veins avoided complications of central lines required for TPE and reduced hospital stays. We suggest that early addition of danazol and early switching from TPE/FFP to the new regimen would benefit patients with TTP. However, a larger-scale randomized prospective study is needed to rigorously evaluate the efficacy and indications for this regimen.

Thrombopoietin Stimulation Leads to Enhanced Polyploidization in p53-/- Bone Marrow Megakaryocytes: In Vivo and in Vitro Studies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2531-2531
Author(s):  
Pani A. Apostolidis ◽  
Stephan Lindsey ◽  
William M. Miller ◽  
Eleftherios T. Papoutsakis
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Reticulated Platelets ◽  
High Ploidy ◽  
And Control ◽  
Platelet Formation

Abstract Abstract 2531 Poster Board II-508 BACKGROUND AND HYPOTHESIS. We have previously shown that tumor suppressor p53 is activated in differentiating megakaryocytic (Mk) cells and its knock-down (KD) leads to increased polyploidization and delayed apoptosis in CHRF, a human Mk cell line. Furthermore, bone marrow (BM)-derived Mks from p53−/− mice reach higher ploidy classes in culture. Accordingly, we hypothesized that the role of p53 during megakaryopoiesis is to delimit polyploidization and control the transition from endomitosis by inhibiting DNA synthesis and promoting apoptosis. Here, we test this hypothesis by examining the differential effect of mouse thrombopoietin (rmTpo) on the ploidy of p53−/− and p53+/+ mouse Mk cells. METHODS. 8–10 week-old, male p53−/− mice and p53+/+ littermates were injected once with 1.2 μg rmTpo or saline. On days 2 and 5 after Tpo/saline treatment, tail-bleeding assays were performed to measure bleeding times/volumes, mice were bled for platelet counts and sacrificed to harvest BM. We employed flow cytometry to examine baseline ploidy in BM-resident Mks in p53−/− and p53+/+ mice as well as Mk cells generated from BM progenitors after 4 and 6 days of culture with rmTpo. RESULTS. At steady state, ploidy in BM-resident CD41+ Mk cells was similar in p53−/− and p53+/+ mice: 11.8±2.3% and 10.7±1.3% of p53−/− and p53+/+ Mks, respectively, reaching a ploidy of ≥32N (n=3-4). Platelet counts were 1.3×106±1×105/μl (12.5±1.0% reticulated) and 1.1×106±5×104/μl (12.4±1.3% reticulated) in p53−/− and p53+/+ mice, respectively (n=8). Two days following Tpo treatment of the mice, we did not observe significantly increased platelet levels, while ploidy was marginally affected. However, 5 days following Tpo treatment, we found greater ploidy in the BM in the absence of p53: 22±1.6% 16N and 10.1±0.8% ≥32N Mks in the p53−/− versus 18.6±3.3% 16N and 7.1±1.4% ≥32N Mks in the p53+/+ (n=2). This was accompanied by increased platelet formation: 23.6±8.3% reticulated platelets in the p53−/− versus 17.8±2.6% in the p53+/+ (n=2). Culture of BM cells from non-Tpo treated mice with 50ng/ml rmTpo resulted in a 50% increase in total Mks and increased polyploidy by day 6 of culture: 38.6±4.6% of p53−/− versus 19.2±2.3% of p53+/+ Mks reached ploidy classes of ≥32N (n=3-4, p < 0.01). Lack of p53 led to hyperploid Mk cells; by day 6 of culture 10.3±2.2% of p53−/− Mks were in ploidy classes of 128N and higher, while only 0.6±0.1% p53+/+ Mks achieved such high ploidy (n=3-4). In addition, a 6 day culture with Tpo of BM cells derived from p53−/− and p53+/+ mice pre-treated with Tpo 5 days prior to sacrifice led to more profound polyploidization compared to Mks generated from the non-Tpo treated mice but only in the p53−/− Mks: 48.8±1.1% of p53−/− versus only 17.6±0.2% of p53+/+ Mks reached ploidy ≥32N (n=2). Microarray analysis comparing p53KD to control CHRF cells undergoing Mk differentiation revealed down-regulation of genes coding for platelet surface complex CD41/CD61 and CD62P in the p53KD cells. To examine the possibility of altered functionality of platelets in p53−/− mice, we performed tail-bleeding assays on the mice that did not receive Tpo. Bleeding times and volumes were generally prolonged in the absence of p53 (all p53−/− mice exceeded the 10 min duration of the assay; mean p53−/− and p53+/+ blood loss was 17μl and 10μl, respectively, n=3-4). CONCLUSIONS. Our data indicate that in vivo polyploidization and platelet formation from Mks is increased in the p53−/− relative to p53+/+ mice after Tpo administration. These data are in line with our hypothesis that p53 activation decreases the ability of Mks to respond to Tpo and undergo polyploidization. Additionally, our preliminary data on platelet functionality suggest that p53 may have a role in hemostasis. Disclosures: No relevant conflicts of interest to declare.

Analysis of Spanish Experience During Imiglucerase Shortage

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4725-4725
Author(s):  
Pilar Giraldo ◽  
Pilar Irún ◽  
Pilar Alfonso ◽  
Jaime Dalmau ◽  
MAngeles Fernández-Galán ◽  
...  
Keyword(s):  
Haemoglobin Level ◽  
Gaucher Disease ◽  
Bone Pain ◽  
Position Statement ◽  
Activity Increase ◽  
Platelet Counts ◽  
Enzyme Replacement ◽  
European Working ◽  
Before And After ◽  
Risk Patients

Abstract Abstract 4725 In the last twenty years enzyme replacement therapy (ERT) with imiglucerase has been a clinically effective for Gaucher disease (GD). The recombinant glucocerebrosidase administered intravenously - usually at biweekly intervals by lifelong has improved the quality of life of patients, avoided spleen removal and bone complications. In the last months an acute shortage of imiglucerase manufactured by the Genzyme Corporation (MA, USA) has occurred as a result of viral contamination firstly and other deficiencies in the production facility. In September 2009 a position statement based on the findings of the European Working Group for Gaucher Disease and European Gaucher Alliance, established a set of key recommendations about identification and monitoring of at-risk patients threatened. In Spain the follow-up of patients and the strict complementation of rules of therapy have permitted to obtain a profile of the situation in a group of patients with restricted ERT. Patients and Methods: A total of 50 GD1 patients have been analyzed before and after 6 and 12 months of imiglucerase shortage. Have been excluded for analysis children in order to dose reduction has been minimal as well as patients who have switched to another ERT or miglustat therapy. Results: Gender: 25 males/25 females. Mean age of group: 45.3±15.3 (range:18-84) SSI at diagnosis(Dx): 8.7±3.8 (range:3-19) Chitotriosidase (CT) activity at Dx:13,383±12,783 nM/mL.h; CCL18/PARC at Dx: 767±1,198 ng/mL. 20% of patients were splenectomized and 78% had bone disease at Dx. During shortage 23 patients (46%) discontinued therapy, in this period only one patient suffered a bone crisis and other anaemia as complications. Mean reduction of haemoglobin level: 2.7% (NS), platelet counts: 5.4% (NS). CT activity was increased 135% (p<0.03) and CCL18/PARC 8.2% (p<0.08). In 17 patients (34%) imiglucerase was reduced at 50%, in this period seven patients (41.0%) suffered a bone pain and four patients (23.5%) required support therapy. Mean reduction of haemoglobin level 2.9% (NS), no changes in platelet counts. CT activity increase 48.2% (p<0.03) and not changes in CCL18/PARC concentration was observed. In addition in 3 patients (6%) the reduction was 75% and 7 patients (14%) switched to another ERT (4 patients) or miglustat (3 patients). Conclusions: In our experience, the shortage of imiglucerase in the last months has produced a incidence in bone pain of 20% and one case with anaemia and significant increase of CT activity and no significant changes in blood counts and CCL concentration, 14 % patients has required switch another therapy. Disclosures: Off Label Use: Lenalidomide is not approved for the treatment of smoldering multiple myeloma.

Gaucher Disease and Multiple Myeloma: A Diagnostic and Treatment Challenge

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2166-2166 ◽  
Author(s):  
Hanna Rosenbaum ◽  
Irit Avivi ◽  
Eliezer A. Rachmilewitz ◽  
Paulina Petchenko
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Avascular Necrosis ◽  
Gaucher Disease ◽  
Laboratory Data ◽  
Type I ◽  
Intensive Chemotherapy ◽  
Pathological Fractures ◽  
Severe Pancytopenia ◽  
Bone Complications

Abstract Abstract 2166 Background: Type I Gaucher disease (GD) is characterized by hepatosplenomegaly, pancytopenia and skeletal complications. Pancytopenia is attributed to the infiltration of bone marrow with the lipid laden Gaucher cells, fibrosis and hypersplenism. Bone involvement includes osteopenia, osteolytic lesions, pathological fractures, infarcts and avascular necrosis. Association between Type I Gaucher disease (GD) and hematological malignancies was suggested in several reports. Coexistence of GD and multiple myeloma (MM) was the most common neoplasm. Diagnosis of MM in GD patients is challenging due to the difficulty in identifying myeloma cells in the bone marrow heavily infiltrated with Gaucher cells, requiring immunohistochemistry, immunophenotyping, as well as molecular and cytogenetic evaluations. Bone complications in GD and MM may be similar, hindering the differential diagnosis of the two states. Treatment is also challenging because of the possible prolonged pancytopenia following intensive chemotherapy. The current study has summarized diagnostic and treatment approaches in patients with concomitant GD and MM. Methods and patients: Clinical and laboratory data of the cohort of 160 Type I GD patients followed at the Department of Hematology of the Rambam Medical Center (Haifa, Israel) were analyzed aiming to evaluate the incidence of MM and management of the disease in this specific population. Results: Among the 160 GD patients, 6 (3.7%) were diagnosed with MM. Five were males and one female, with a median age of 65 years (range 38–87) at diagnosis of both GD and MM. All these patients were of Ashkenazi descent, homozygous for N370S mutation and presented with moderate to severe pancytopenia at diagnosis. In 5/6 individuals, MM and GD were diagnosed concomitantly at presentation and only 1/6 developed MM during the follow up of known GD. The MM subtype included: IgGk (n=3) IgAl(n=1) and IgAk (n=2). Bone complications were found in all the 6 patients, including severe osteoporosis, lytic lesions and pathological fractures, which may be related to both GD and MM, while bone infarcts and avascular necrosis were typical of GD only. In one patient with resistant course of MM successful autologous peripheral stem cell transplantation (APBCT) was performed following intensive chemotherapy. Enzyme replacement therapy (ERT) which was initiated shortly after APBCT resulted in significant improvement in the response to MM treatment. Two other elderly patients were treated with melphalan and prednisone (in the pre-ERT era), resulting in a stable MM course. Three patients received ERT only for symptomatic GD and remained stable regarding MM, with an improvement in their GD status. Conclusion: GD appears to be associated with a higher incidence of MM compared to that reported for general population. Both diagnosis and treatment are challenging, given the presence of Gaucher cells in the bone marrow, interfering with identification of MM cells and resulting in pancytopenia, which makes treatment for MM more complicated and less effective. Therefore, therapy should include a combination of chemotherapy and ERT to prevent prolonged severe pancytopenia in GD and MM patients who are resistant to treatment. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document