Coincidence of Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM) in One Patient: An Exceptional or Common Event? Summary of 4 Cases at a Single Center.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4980-4980 ◽  
Author(s):  
Justyna Rawluk ◽  
Percy Schröttner ◽  
Ullrich Denz ◽  
Dietmar Pfeifer ◽  
Milena Pantic ◽  
...  

Abstract The simultaneous appearance of B-CLL and MM in the same patient (pt) seems to be a rare phenomenon. In those cases - our experience included - 1. the myeloma exhibits an aggressive course, 2. with CLL-treatment, MM seems to emerge, 3. which, if well treated (e.g. high-dose chemotherapy [CTx] with autologous peripheral blood stem cell transplantation [auto-PBSCT]), may lead to a slower myeloma course, improved clinical condition and CLL disapearance. Here we report on the simultaneous (n=2) and successive (n=2) occurrence of CLL and MM in four pts, who were diagnosed at our center during the last year. We suggest that the occurrence of CLL and MM, when carefully monitored, may be more frequent than assumed so far. Case 1. This 64-year-old male was evaluated due to weight loss, leukocytosis, anaemia, foamy urine and increased creatinine. Kappa (k) Bence-Jones (BJ) proteinuria and elevated k-serum free light chains (SFLC) were found. A bone survey was normal, but BM biopsy showed infiltrates of plasma- (PC) and B-CLL-cells. Due to Rai 0 CLL and MM stage IIIB, the pt received 2 cycles of VAD followed by an auto-PBSCT. Thereby, he obtained a PR. Maintenance with thalidomide stabilized both diseases. Case 2. This 77-year-old male was simultaneously diagnosed with RAI 0 CLL and stage IIIB MM. Diagnostics revealed a lambda (l)-paraprotein, BJ-l-proteinuria and lytic bone lesions. The BM showed monoclonal l-LC-expressing PCs, and k-LC-CLL-cells. The pt received melphalan/prednisone (MP) and thereby obtaining SD. Case 3. This 62-year old pt was diagnosed with RAI II B-CLL. Two years later, he showed increased splenomegaly, anemia, elevated l-SFLC and dense CLL-BM-infiltrates. Chlorambucil/prednisone-CTx was initiated, but failed to improve his condition. Further evaluation due to renal impairment revealed multiple lytic lesions and monoclonal l-LC-expressing PCs, coexisting with remaining CLL infiltrates in his BM. Cyclophosphamide-CTx, 2 cycles of VAD and auto-PBSCT were performed and Bortezomib maintenance, improving the pt’s general condition, his PB counts and l-SFLC secretion. Despite these efforts, MM relapse occurred 5 months later with persisting absence of his preceding CLL and the pt eventually died due to myeloma progression. Case 4. This 73-year-old male was diagnosed with B-CLL, showing moderate splenomegaly, lymphocytosis, initially not requiring any therapy. Two years later, he showed a deteriorating clinical condition, multiple osteolytic lesions, anemia, hypercalcemia, monoclonal IgA paraprotein and k-BJ-proteinuria. A BM biopsy confirmed k-LC B-CLL- and k-PC-infiltrates. The diagnosis of stage IIIA IgA k-MM, and RAI II B-CLL led to MP-CTx that induced SD of his MM and CLL. In summary, our 4 pts had a median age of 69 years (range; 62–77) and showed a median time interval of their CLL and MM diagnosis of 11 months (0–31). All pts had stage III MM and renal impairment in 3/4, whereas CLL showed an indolent course. LCs of CLL and MM were different in all except one pt. Cytogenetic and genomic analyses are currently ongoing and will be reported at the meeting. We conclude that the elucidation of the coincidence of CLL and MM will allow to understand why and how often both occur and also, how they can be efficiently treated. The question of their clonal relationship should be answered via genomic analyses that will allow to gain further insight into the origin of both diseases.

2021 ◽  
pp. 1-5
Author(s):  
Vitaliy Sazonov ◽  
Zaure Tobylbayeva ◽  
Askhat Saparov ◽  
Bolatbek Jubaniyazov ◽  
Samat Issakov ◽  
...  

Background: High-dose methotrexate (HDMTX) is likely to cause a number of side effects and manifest itself as hepatotoxicity, nephrotoxicity, mucositis, and neurotoxicity. A several studies demonstrated the efficacy of extracorporeal detoxification methods such as plasma exchange, hemodialysis (HD), HD filtration, and hemoperfusion for the treatment of MTX delayed clearance. However, none of the existing methods as effective as expected and limited for general implementation due to a procedure-related complication. Case Report: Here, we report a successful implementation of HA-230 hemoadsorption procedure to remove cumulated MTX from the body and reduce its toxicity in a child with ALL after high-dose chemotherapy. Results and Conclusion: Based on our results, single-hemoadsorption procedure with the HA-230 adsorber in case of delayed methotrexate clearance was safe and well-tolerated in a pediatric patient with ALL and would significantly improve the patient’s condition. Further studies need to demonstrate its safety and efficacy in a large number of pediatric patients.


Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 360-367 ◽  
Author(s):  
Angela Dispenzieri

Abstract POEMS syndrome is defined by the presence of a peripheral neuropathy (P), a monoclonal plasma cell disorder (M), and other paraneoplastic features, the most common of which include organomegaly (O), endocrinopathy (E), skin changes (S), papilledema, edema, effusions, ascites, and thrombocytosis. Virtually all patients will have either sclerotic bone lesion(s) or co-existent Castleman’s disease. Not all features of the disease are required to make the diagnosis, and early recognition is important to reduce morbidity. Other names for the syndrome include osteosclerotic myeloma, Crow-Fukase syndrome, or Takatsuki syndrome. Because the peripheral neuropathy is frequently the overriding symptom and because the characteristics of the neuropathy are similar to that chronic inflammatory demyelinating polyneuropathy (CIDP), patients are frequently misdiagnosed with CIDP or monoclonal gammopathy of underdetermined significance (MGUS)-associated peripheral neuropathy. Not until additional features of the POEMS syndrome are recognized is the correct diagnosis made and effective therapies initiated. Clues to an early diagnosis include thrombocytosis and sclerotic bone lesions on plain skeletal radiographs. Therapies that may be effective in patients with CIDP and MGUS-associated peripheral neuropathy (intravenous gammaglobulin and plasmapheresis) are not effective in patients with POEMS. Instead, the mainstays of therapy for patients with POEMS include irradiation, corticosteroids, and alkylator-based therapy, including high-dose chemotherapy with peripheral blood stem cell transplantation.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4830-4830
Author(s):  
Martina Kleber ◽  
Gabriele Ihorst ◽  
Christian Jakob ◽  
Peter Liebisch ◽  
Bernd Koch ◽  
...  

Abstract Renal impairment (RI) of varying severity including end stage renal disease is a common manifestation of multiple myeloma (MM). Nevertheless, the influence of milder - and via creatinine (crea) determination invisible - RI as a risk factor in MM patients (pts) is less well defined. We have previously reported in 167 cancer pts that estimating the glomerular filtration rate (eGFR) as compared to serum crea- or cystatin-levels determines prognostically adverse risk groups (Ann Oncol18: 950–8, 2007). In order to analyze the frequency of RI stages in a homogenous pt group, we determined RI in 198 consecutive MM pts receiving standard (Std; n=103) or high-dose chemotherapy (hd-CTx; n=95) in a multi-center study. We analyzed disease-stage, sex, age, performance status, β2-microglobulin, serum crea and GFR calculated by both the four-component “Modification of Diet in Renal Disease” (MDRD) and Cockcroft-Gault (CG). Evaluated outcomes were overall survival (OS) and progression free survival (PFS). Of note, although median crea, MDRD- and CG-eGFR-values appeared almost normal with 0.9mg/dl, 87 and 82ml/min/1.73m2, respectively, RI as determined as advanced chronic kidney disease (CKD stage >3 = eGFR<60) was apparent in 25% of all pts. We also observed distinct differences in pts receiving Std vs. hd-CTx: the median age was higher with 67 years (y) in the Std vs. 57y in the hd-CTx group (p<0.05). Advanced disease, as defined as number of pts with Durie & Salmon stage II/III, was comparable in both groups (92 vs. 97%, respectively). Although the crea was still within normal ranges in the Std- (1mg/dl) vs. hd-CTx-pts (0.8mg/dl), MDRD- and CG-formulas uncovered relevant differences between both groups: both MDRD- and CG-eGFRs being significantly decreased in Std- vs. hd-CTx-pts (MDRD: 72 vs. 96; CG: 68 vs. 101, respectively; p<0.05). Correspondingly, more Std-pts showed a decreased eGFR <60 than hd-CTx-pts (34 vs. 14%). Comparing solely those Std vs. hd-CTx-pts with active, progressing and/or proliferating myeloma also ascertained significant eGFR-differences in terms of decreased MDRD- and CG-levels, as well as more pts with CKD stage 3–5 in the Std group. This suggests that these MM pts had a significantly different renal function in Std-pts, most reliably, however, only detected via eGFR and CKD staging assessment, rather than the serum crea alone. Associated with RI (eGFR <60), PFS and OS were significantly decreased as compared to eGFR values >60 with estimated median values of 15 vs. 20 months and 36 vs. 61.3 months, respectively (p<0.05). In line, PFS and OS for Std- and hd-CTx-pts for eGFR<60 were considerably lower as compared to pts with eGFRs>60. In conclusion, we highlight the importance of efficiently detecting RI by means of eGFR-assessment, which allows to detect MM pts with mild - and/or via crea determination invisible - RI. Our data demonstrate that eGFR-decline substantially diminishes PFS and OS in consecutive MM pts, and suggest that with RI, Std- as opposed to hd-therapies do not substantially improve PFS/OS, so that novel therapy approaches are especially needed for those pts with RI, not receiving hd-CTx. These findings should also hold true for other cancer pts.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5009-5009
Author(s):  
Neetu Radhakrishnan ◽  
Mark A. Hoffman

Abstract A 53 year old man with Rai stage IV CLL was being treated with R-HyperCVAD when he presented between cycles with fatigue, lethargy and pancytopenia. Clinical examination revealed diffuse adenopathy and splenomegaly. Serum calcium was 13.6 mg/dl, phosphorus level was 2.7 mg/dl, and alkaline phosphatase was 54 U/L. PTH was 4 Units/L (10–65), PTHrP &lt; 0.2 pmole/L (0–1.9), 1–25 (OH) Vitamin D &lt; 10pgm/ml (22–67). Quantitative immunglobulins: IgA 10 mg/dl, IgG 252 mg/dl, IgM 50 mg/dl. Immunofixation revealed a faint IgG lambda paraprotein. There were no lytic lesions on skeletal survey. Bone marrow biopsy revealed focal large cell transformation (Richter’s syndrome). Cytogenetics revealed 3 metaphases with complex cytogenetic abnormalities, indicating clonal evolution. The hypercalcemia resolved with appropriate therapy, but despite subsequent treatment with CAMPATH, he died 2 weeks after diagnosis. A review of reported patients with CLL and hypercalcemia in the literature was performed from 1980 onwards using MEDLINE and PubMed; only those cases in which clinical aspects, biochemistry, PTH levels, imaging studies and concurrent pathology (if obtained) were documented, are summarized in this analysis (n=13). Rai stage: I n=1, II n=4, III n=3, IV n=5. Immunoreactive PTH levels were low or normal in 100% of patients. In 5 cases in which it was measured, 1–25 (OH) Vitamin D levels were not elevated. PTHrP was normal in 2 cases and elevated in 1. In nine patients, multiple lytic bone lesions were present on skeletal radiology. Two patients had osteopenia without lytic lesions. Two had no lytic lesions. Six of ten patients had evidence of transfomation on lymph node and/or bone marrow biopsy performed at the time of evaluation for hypercalcemia. Prognosis was poor (range 0.5–12 months) with only one patient surviving post allo-transplant. In conclusion, hypercalcemia in CLL is rare. Osteolytic lesions are present in the majority of cases. PTH levels are low, and thus this hormone is not mediating the hypercalcemia. The evidence is also against a role of elevated Vitamin D. Histological transformation is seen in half of the cases. Survival is poor after diagnosis of hypercalcemia. The mechanisms(s) of the osteolysis and hypercalcemia remain to be defined.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3399-3399
Author(s):  
Meletios A. Dimopoulos ◽  
Anastasia Pouli ◽  
Athanasios Angnostopoulos ◽  
Panagiotis Repoussis ◽  
Argyris Symeonidis ◽  
...  

Abstract Introduction: Most patients with multiple myeloma (MM) present with multiple lytic bone lesions, extensive marrow plasmacytosis and anemia. Furthermore in several of them hypercalcemia and renal impairment are evident at diagnosis. Over the years, we have seen occasional young patients with MM who presented with multiple lytic bone lesions but without intervening infiltration of bone marrow i.e. a pattern consisting of macrofocal MM. Patients and methods: In order to assess the clinical and laboratory features and the outcome of patients with macrofocal MM we performed a retrospective analysis of symptomatic patients with MM ≤40 years of age at diagnosis who received primary treatment over a 20 year period (from January 1, 1985 to December 31, 2004). The diagnosis of macrofocal MM required the presence of lytic bone lesions and the absence of obvious bone marrow plasmacytosis (BMPC&lt;10%) on bone marrow aspirate and/or biopsy. Results: Among 51 patients ≤40 years at the time of initial treatment, 10 patients fulfilled the criteria of macrofocal MM. Patients’ median age, gender, myeloma heavy and light chain were similar among patients of the 2 groups. When compared with patients with typical MM, patients with macrofocal pattern were less anemic (p=0.018), none had hypercalcemia (p=0.1), renal impairment (p=0.17), elevated serum LDH (p=0.14), or stage 3 according to the International Staging System (ISS) (p=0.13). Four of the 10 patients with macrofocal MM versus 0 of 41 patients with typical MM (p=&lt;0.01) had a prior diagnosis of solitary bone plasmacytoma. Approximately 80% of patients in both groups received primary treatment based on high-dose dexamethasone regimens (VAD or VAD-like regimens). An objective response was noted in 55% of patients with macrofocal MM and in 50% of patients without this pattern. The median survival of patients with typical MM was 57 months and has not been reached in patients with macrofocal MM (p=0.087). In the latter group of patients, median survival is projected to exceed 8 years. The 10 year survival rate is 20% and 5% in patients with or without macrofocal myeloma respecrively. Conclusion: Our analysis indicates that macrofocal MM is a distinct entity in young patients with MM. Despite multiple lytic bone lesions, such patients have features of low tumor burden and an improved survival when compared with young patients with typical MM. Future studies including gene profiling may reveal potential biological differences among the two groups of patients.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3341-3341
Author(s):  
Robert C. Kane ◽  
Robert G. Pratt ◽  
Susan Lu ◽  
Ann T. Farrell

Abstract Background: RPLS while historically uncommon and not well understood, is an important entity for hematology-oncology clinicians since this syndrome is being encountered more frequently and prompt recognition and management can allow full recovery for most patients. RPLS is considered a capillary leak syndrome affecting the brain and is associated with hypertension and fluid retention. RPLS is distinct from hypertensive encephalopathy. Antecedent blood pressure increases are not always abrupt or dramatic. RPLS should be considered when patients who are receiving various classes or regimens of cancer treatments report acute onset of headache and visual impairment, lethargy, confusion, seizure, or other neurologic disturbances. The complication occurred in less than 0.1% of patients receiving bevacizumab in clinical studies. The most important physical examination findings are a distinct increase in blood pressure as compared to the patient’s usual range, along with visual impairment. The diagnosis is usually confirmed by the MRI finding of bilateral posterior cerebral white matter edema. Methods: We searched the FDA Adverse Event Reporting System (AERS) database of post-marketing safety reports for the 10 year period 1997 through July 2007 for all submitted reports identified by the MedDRA preferred term “reversible posterior leukoencephalopathy syndrome” or similar terms for diagnosis in association with cancer therapy. We excluded reports involving use of an anti-neoplastic agent for a non-cancer diagnosis and reports involving the concomitant use of an immunosuppressive agent. Results: Among 109 cases reported in the 10 year interval, 64% (70/109) of the reports were received in the last 18 months of the time interval. The age range was 3 – 84 years; 30% of patients were male and 70% were female. Among 10 fatal outcomes, four appeared temporally associated with RPLS. Colorectal cancer was the most common underlying disease in 17% of the cases (19/109); the next two most common cancer settings were lymphoma 13% (14/109) and acute lymphocytic leukemia 11% (12/109). Bevacizumab (33) was the most commonly reported drug, followed by vincristine (31), cyclophosphamide (20) prednisone (20), oxaliplatin (18), fluorouracil (18), and dexamethasone (17). Regimens of CHOP or CVP were reported in 13 cases and vincristine plus steroid plus asparaginase in 9 cases. Conclusions: Recognition and reporting of RPLS in association with chemotherapy is increasing, in part due to increasing use of anti-angiogenic therapies which raise blood pressure. Causality is not implied by association. Close monitoring of blood pressure is important, especially for agents inhibiting the VEGF pathway and for protocols mandating high fluid infusion volumes. Prompt control of blood pressure, correction of fluid and sodium overload, and cessation of the anti-cancer agent are usually successful in allowing recovery. No therapies for RPLS have been studied prospectively. High dose steroids may not be appropriate in view of their known effects to elevate blood pressure, to expand plasma and total body fluid volumes, and their association above. The risk of reinitiating therapy in patients previously experiencing RPLS is not known.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10694-10694
Author(s):  
S. Farjami ◽  
F. Waheed ◽  
D. Liu ◽  
K. Seiter ◽  
T. Ahmed

10694 Background: Despite the improvements related to introduction of neoadjuvant chemotherapy, the prognosis of patients with inflammatory breast cancer remains poor. The purpose of this study was to evaluate the efficacy, feasibility and outcomes of high dose chemotherapy in this group of patients. Methods: Between June 1991 and January 1999, twenty eight patients with pathologically confirmed inflammatory breast cancer were consecutively enrolled in this study. All patients were rendered free of clinically evident disease by using chemotherapy (adjuvant, neoadjuvant or both) either alone or in combination with surgery. Following stem cell collection patients received HD-CT with thiotepa 250mg/m2 days 1, 2 & 3(total dose of 750mg/m2), mitoxantrone 40mg/m2 on day 1 and carboplatin 333mg/m2 on days 1, 2 & 3 ( total dose of 1gm/m2). Previously stored stem cells were infused on the seventh day of HD-CT chemotherapy. Eligible patients received radiation to the chest wall and tamoxifen for 5 years. Results: With median duration of follow-up of 46.9 months( range 15.1–177.2), the median overall survival (OS) and progression free survival (PFS) were 42.5 months (range 9.7–135.7) and 34.8 months (range 3.3–135.7), respectively. The multivariate analysis showed a significantly better EFS and OS in patients with estrogen receptor (ER) positive tumors ( P value ≥ 0.003). Mucositis and Infection were the most severe non-hematological toxicities. Grade four cardiac and pulmonary toxicities developed in one patient. There was no transplant related mortality. One patient developed myelodysplastic syndrome. Conclusions: The results of our study suggest that high dose chemotherapy with thiotepa, mitoxantrone and carboplatin is a safe and efficacious regimen in patients with stage IIIB inflammatory breast cancer. No significant financial relationships to disclose.


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