Over a period of 28 months, we observed five cases of osteonecrosis of the jaw (ONJ) in cancer patients treated with bisphosphonates (BP) at our institution. This prompted us to undertake a retrospective, multicenter study to analyse the characteristics of patients who exhibited ONJ and to define the frequency of ONJ in multiple myeloma (MM). We identified 35 cases in Gruppo Italiano Studio Linfomi centers during the period 2002 - 05. The median time from cancer diagnosis to the clinical onset of ONJ was 70 months. In these 35 cases of ONJ, 24 appeared 20 - 60 months after starting BP treatment. The time for the onset of ONJ was significantly shorter for patients treated with zoledronic acid alone than for those treated with pamidronate followed by zoledronic acid. The frequency of ONJ in the MM group during the study period was 1.9%, although the nature of the present study may have resulted in an underestimation of ONJ cases. Our analysis strongly suggested an association between the use of BP and the occurrence of ONJ, although we were unable to identify any definite risk factors with a retrospective study. The most frequently ONJ-associated clinical characteristics were chemotherapy treatment, steroid treatment, advanced age, female sex, anemia, parodonthopaties/dental procedures and thalidomide (in the case of MM patients).

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Although the evidence available associating bisphosphonates (BP) with osteonecrosis of the jaw (ONJ) is far from conclusive, the growing literature reports strongly suggest a strict relationship between them. The real frequency of this complication is unknown because of the recent observation of this condition, the bias related to retrospective studies and the wide-spread use of this supportive therapy. Aims of this research were to look for additional risk factors for developing ONJ and to determine the frequency of this event in the subgroup of patients affected by Multiple Myeloma (MM) treated with BP. We asked 49 GISL centers to participate in a retrospective multicenter study filling out a form containing several queries, including sex and age, anamnesis for smoke habit, anemia and thrombotic events, type and time of neoplasia diagnosis, treatment and neoplasia status, odonthoiatric anamnesis, type and duration of therapy with BP, microbial isolation in site of lesion, specific treatment for osteonecrosis, number of patients (pts) affected by MM treated with BP from 2002 to 2005. Fifteen centers decided to participate in the study and 12 had cases of osteonecrosis. ONJ was reported in 19 pts. Sixty % were females and the median age was 65 ys. Sixteen had MM, 1 breast cancer, 1 prostatic cancer, 1 osteoporosis steroid related. Median time from diagnosis of cancer was 54 months and median duration of treatment with BP was 34 months. Thirteen events manifested between 20 and 60 months. Of the 19 pts, 8 had received zolendronate, 2 pamidronate and 9 both drugs. None had radiotherapy on head and neck, while two received total body irradiation. In these two cases, ONJ was associated with necrosis of the pelvis. The 2 solid tumors were treated with ormonal therapy. All MM pts had received one or more line of treatment including, VAD, MP, steroids and thalidomide alone or in combination, as well as high dose melphalan, as part of autologous bone marrow transplant. ONJ involved the mandible in 14 pts, the maxilla in 3 and both in 2. Symptoms included local pain and discomfort. In 17 cases CT scan was the strumental procedure used to identifiy the lesion. In 14 pts biopsy was performed excluding localization of neoplasia in 11 cases. Microbiological evaluation of the lesion was positive in 11 pts, with 6 cases of Actynomices. In 12 patients ONJ was apparently spontaneous; in 7 occurred after dental procedures. Parodonthopaties were present in 10 pts. In 11 cases ONJ was complicated by fistula, exposed bone or abscess. BP were stopped in 17 pts. Antibiothic therapy was administered in 17 cases; 7 pts underwent hyperbaric oxygen therapy and 8 surgical debridement. Several pts improved but none were cured. Considering only the MM subgroup 16 cases of ONJ were identified among 888 pts treated with BP between 2002 and 2005, with a frequency of 1.8%. Utilizing the data collected by our retrospective study a fine statistical analysis is not applicable. However, in MM pts the frequency of steroid treatment, parodonthopaties and anemia was particularly high, respectively 100%, 56%, and 56%, supporting the idea that these are additional risk factors for developing ONJ.

It is generally assumed that chronic lymphocytic leukemia of B cell origin (B-CLL) is characterized by the presence of surface membrane immunoglobulins (SmIg) and by the absence of cytoplasmic immunoglobulins (CyIg). In a variable number of cases SmIg are not detectable because of their low density on the cellular surface. Because a constant presence of CyIg in 20 subjects suffering from B-CLL has been reported recently, we reexamined 15 SmIg-negative and 10 SmIg- positive B-CLL patients by SmIg and CyIg determinations. We used a direct immunofluorescence method on peripheral blood mononuclear cells for the detection of SmIg and, after fixation, for CyIg. CyIg were detectable in 24 out of 25 cases, with a fluorescence intensity ranging from weak to moderate. The existence of frequent negative results for CyIg determination in B-CLL reported in the literature probably depends on the low sensitivity of the method used. We conclude that CyIg determination is useful in phenotyping every B-CLL patient, especially SmIg-negative ones.

Idiopathic thrombocytopenic purpura (ITP) during pregnancy may cause serious bleeding in the mother and fetus. Therapy with high-dose intravenous immunoglobulins has caused an immediate and predictable rise in platelet count in both adults and children with chronic or acute ITP. We report our experience in managing a woman near term in pregnancy. The patient demonstrated a rapid increase in platelet count, delivered without excessive bleeding and had a normal child with normal platelet count. Intravenous immunoglobulins may offer a new and safe way to control maternal and fetal platelet counts during pregnancy, delivery and neonatal period.