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Oral therapies have become a common treatment choice for several lymphoid cancers. While therapeutic efficacy and patient preference for this therapy type have been reported, there is a lack of knowledge about its effectiveness for lymphoma in clinical practice, particularly in regard to the effects of medication nonadherence. While studies of oral medications in other diseases have shown that adherence is a major factor in outcomes and costs, there is scant research investigating adherence specifically in lymphoma patients, who face unique challenges in their diseases and treatments. To address the limited data available, we constructed a conceptual model and highlighted key opportunities for future research to better elucidate oral therapy adherence in lymphoma. This research will hopefully improve understanding and efficacy of oral treatment for lymphoma patients, while also informing other cancers utilizing oral therapies currently and in the future.

Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL. Overall response rate to frontline therapy was 69%, and 76% of patients subsequently received allogeneic stem cell transplant (ASCT). After a median follow-up of 11 months, median progression-free survival was 15 months and median overall survival was not reached. In conclusion, FGFR1-rearranged hematologic malignancies present with features of MPN and/or AL. FGFR1 and RUNX1 are therapeutic targets for ongoing and future clinical trials.

Introduction: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments., Patients and Methods: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR])., Results: Patients who did not achieve a CR or PR did not respond well to subsequent treatments. Malignancies following bendamustine were diagnosed in 11% (21) of patients (first line [7] and salvage [14]), including squamous (8) or basal cell (4) skin cancers; prostate cancer (3), renal cancer (3), bladder cancer (2), melanoma (2), lung cancer (1), and histiocytic sarcoma (1). There were no occurrences of therapy-related myelodysplastic syndrome or acute myelogenous leukemia reported. Infections occurred in 63% of patients; however, no deaths were attributable to bendamustine., Conclusion: Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To investigate the dynamic change of follicular T helper cells (T FH ) in patients with malignant lymphoid disease (MLD) and to explore its clinical significance., Methods: The dynamic change of T FH cells, ICOS + - and PD-1 + T FH cells at pretreatment and different treatment periods was determined by flow cytometry in 85 MLD patients. Concentration of interleukin 21 (IL-21) was evaluated by ELISA, and the correlation between clinical prognosis and the ratio of T FH cells was analyzed., Results: Significantly increased ICOS + - and PD-1 + T FH cells were found in MLD patients at pretreatment compared to healthy controls. Decreased or even close to normal levels of ICOS + - and PD-1 + T FH cells were found at the end of treatment. However, in the patients with progressive disease, high levels of ICOS + - and PD-1 + T FH cells were found. Moreover, a significantly increased plasma IL-21 level was found in MLD patients. Negative correlation was found between the level of ICOS + -, PD-1 + T FH cells, as well as IL-21 and the prognosis of MLD., Conclusions: Significantly increased T FH cell ratios were found in patients with MLD, and decreased T FH cells ratios could be expected in those treatment-effective patients, which could be used as the therapeutic efficacy index.

Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplant (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight patients with advanced lymphoma underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporine-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years was 25% (95% confidence interval [CI]: 13-40%) and 44% (95% CI: 28-59%), respectively. Previous high-dose therapy and autologous stem cell transplant (HDT-ASCT) and elevated lactate dehydrogenase (LDH) at the time of allo-SCT resulted in inferior OS. Within this cohort of patients with high-risk lymphoma, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of progression of disease, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT.

In the article data are presented about morbidity by oncogematologic pathology - one of the most meaningful of social-economic problems. In Ukraine annually diagnose the to 8 thousand new cases of haemoblastosis. Indexes of morbidity on a 100 thousand population are 5,2; at illness of Hodgkin's lymphoma - 2,5, at plural myeloma - 1,6; at leukemia - 8,1. Morbidity by haematological pathology in Kyiv long time remains high: annually 250 expose patients with malignant lymphnoma, 57 - with myeloma, 190 - with leukemia, from them at 55 % is a sharp form and at 40 % - chronic. The anxiety of doctors causes circumstance that the special treatment is overcome 58,1 % patients by leukemia, 68,6 % - plural myeloma and 77,8 % patients with malignant lymphoma. World experience shows that application of complex methods of therapy allows to prolong life-span 80-90 % patients with Hodgkin's malignant lymphoma on 10, and at 95 % patients by a lymphogranulomatosis - to attain nonrecurrence survival to 5 years.

The Class II human leukocyte antigen (HLA) DRB1 antigen DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-lymphoproliferative disorders. We retrospectively reviewed the role of HLA DR4 on outcomes in 77 related and 22 unrelated consecutive first HLA-matched alloHSCT patients with lymphoid malignancies treated between 1992 and 2003. HLA DRB1 typing was determined by molecular (n = 69) or serologic (n = 30) methods. The proportion of patients with one HLA DR4 antigen was 18% (18/99). At a median follow-up of 5.6 years, there were no significant differences in aGvHD, cGvHD and OS between the HLA DR4 positive versus negative patients in any disease or donor subgroups. Nine of 18 (50%) DR4 positive patients and 20 of 81 (25%) DR4 negative patients had disease progression post HSCT (p = 0.033). Progression-free survival (PFS) at 3 years was 29% in the DR4 positive group and 70% in the DR4 negative group (p = 0.004). In univariate and multivariate analyses, DR4 positivity was the only significant factor associated with PFS (RR = 3.2, p = 0.007). Our results suggest that in addition to the known role of HLA DRB1 disparity in mediating histocompatibility, HLA DR4 is associated with inferior PFS in patients with lymphoid malignancy undergoing alloHSCT.

Forty-one previously untreated children with Stage IV non-Hodgkin's lymphoma were studied from January 1971 to April 1979. All patients had bulky disease histologically proven to be non-Hodgkin's lymphoma with bone marrow involvement. They were separated into two groups according to the extent of bone marrow involvement. Group IVA included 14 patients with 25% or less lymphoblasts in the bone marrow. Group IVB included 27 patients with more than 25% blasts in the marrow. Their clinical characteristics with regard to age, sex, hemogram, histology, primary site, and blast morphology are compared. All were treated with the LSA2-L2 protocol with radiation therapy to one or more bulky sites of involvement. The disease-free actuarial survival for Group IVA was 64% with a median observation time of 49 months while that for Group IVB was 65% with a median observation time of 66 months. There was no statistical difference in the survival rates between the two groups. Hence, we conclude that the extent of bone marrow involvement does not affect the prognosis in Stage IV non-Hodgkin's lymphoma. It appears that radiation therapy may have contributed to the improved survival in our series. Furthermore, a subset of patients in Group IVB (24/27) who could be considered as high-risk acute lymphoblastic leukemia on the basis of age, initial leukocyte count, hemoglobin, mediastinal mass or T- or B-cell markers showed an improved survival (73% versus 43%) when compared to patients treated with conventional leukemia regimens.

Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery.

Forty-eight patients with chronic lymphocytic leukemia (CLL), and 12 patients with small (well differentiated) lymphocytic lymphoma (WDL) were histologically evaluated for their pattern of bone marrow (BM) involvement. Four different types of BM infiltration were recognized: nodular (N), interstitial (I), nodular and interstitial (mixed) and diffuse (D). The pattern of BM involvement was compared with the clinical, laboratory, and survival status in all patients. The extent of the disease in CLL patients, was determined by the Rai and the International Workshop on CLL Staging Systems, while in WDL patients the Ann Arbor staging system was used. In the CLL group the N pattern was found in 8%, the I in 33%, the mixed in 31%, and the D in 27% of the patients. Based on the International Workshop on CLL Staging System, the I pattern of BM involvement was more frequently found in Stage A (56%), the mixed in Stage B (68%), and the D in Stage C disease (90%). All CLL patients with D pattern required treatment from the beginning, contrary to CLL patients with the other patterns, in whom therapy was required in less than 50%. Similarly, deaths were more common in the D pattern in whom therapy pattern than in the other patterns. In the WDL patients BM involvement was found in 4 of 12, (33%) and its pattern of positivity was always nodular, although most patients (10 of 12) had advanced disease. It is concluded that the frequency of BM involvement may contribute in the differential diagnosis of WDL from CLL. In addition, the pattern of BM infiltration correlates very well with the International Staging System for CLL, and the pattern of BM positivity in CLL patients also has prognostic significance.

Four patients with T-cell malignancies of poor prognosis (three with non-Hodgkin's lymphoma and one with acute lymphoblastic leukemia) received the following consolidation therapy for complete or partial remission: cyclophosphamide (120 mg/kg) plus total-body irradiation, followed by reinfusion of cryopreserved autologous marrow previously purged in vitro by immunotoxin T 101 (SR 41322). This immunotoxin is made of the murine monoclonal T 101 antibody coupled to chain A of ricin. The doses of immunotoxin used were 10(-9) and 10(-8) M, and the durations of incubation were 4 and 20 hours at 37 degrees C. Recovery of progenitors CFUc and BFUe was total following incubation with immunotoxin T 101, but diminished after cryopreservation (15%-80% for CFUc, 33%-47% for BFUe), suggesting an increased fragility of the incubated progenitors to freezing. In every case, hematopoietic recovery occurred within normal time periods, with a wbc count greater than 10(9)/L and a platelet count greater than 50 X 10(9)/L on Day 22 (range, 15-31) and Day 21 (range, 22-47), respectively, demonstrating the feasibility of autologous bone marrow transplantation with marrow pretreated by immunotoxin. However, the slow recovery of lymphocytes and the development of severe infections in two patients may indicate that an in-depth study of immunological reconstitution after in vitro treatment of the marrow with immunotoxin T 101 is necessary.

The mortality of patients admitted to intensive care units with haematological malignancy is high. A humane approach to the management of the critically ill as well as efficient use of limited resources requires careful selection of those patients who are most likely to benefit from intensive care. To delineate more accurately the factors influencing outcome in these patients the records of 60 consecutive admissions to the intensive care unit (37 male, 23 female) with haematological malignancy were reviewed retrospectively. Fifty patients were in acute respiratory failure, most commonly (34 patients) with a combination of pneumonia and septicaemic shock. The severity of the acute illness was assessed by the APACHE II (acute physiology and chronic health evaluation II) score and number of organ systems affected. Thirteen patients survived to leave hospital. The mortality of patients with haematological malignancy was consistently higher than predicted from a large validation study of APACHE II in a mixed population of critically ill patients. Moreover, no patient with an APACHE II score of greater than 26 survived. Mortality among the 22 patients with relapsed malignancy (21 deaths), was significantly higher than among the 35 patients at first presentation (26 deaths). On discharge from the intensive care unit all survivors had responded well to chemotherapy and had normal or raised peripheral white cell counts. They included seven patients who had recovered from leucopenia (white cell count less than 0.5 X 10(9)/l). In contrast, 36 of the 47 patients who died were leucopenic at the time of death. The overall mortality of critically ill patients with haematological malignancy is higher than equivalently ill patients without cancer. The dysfunction of an increasing number of organ systems, an APACHE II score of greater than 30, failure of the malignancy to respond to chemotherapy, and persistent leucopenia all point to a poor outcome.

Progress in the study, treatment and cure of hematologic malignancies in children is one of the most gratifying accounts in the entire history of cancer therapy. It is important to note that progress in treatment and cure have been the direct result of formal study of childhood cancers and the development and clinical trial of new treatments designed to improve the response and cure rate. In the experience of the Children's Cancer Study Group (CCSG), approximately half of the children with cancer which are registered have hematologic malignancies. By far the most significant of these is acute lymphoblastic leukemia (ALL), which accounts for 33% of all the cancers registered with the Group. Acute non-lymphoblastic types of leukemia have amounted to 6% of all cancers in our experience, non-Hodgkin's lymphoma for another 6% and Hodgkin's disease for approximately 5%. The cancer death rate in children under the age of fifteen years has declined very significantly in the United States since 1950. In 1955 the National Cancer Institute organized the first national cooperative groups in order to develop and test new treatments for acute lymphoblastic leukemia. The CCSG was the first of these. The success which has been achieved in treating acute leukemia is remarkable, particularly when one recalls that in 1950 the disease was 100% fatal. The death rate due to Hodgkin's disease has also shown a sharp decline, and more recently, deaths due to non-Hodgkin's lymphomas have also declined.

n epidemiologic survey of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) occurring in Israel, Judea, Samaria and the Gaza Strip between the years 1976 and 1981, revealed 205 cases of ALL and 69 of NHL. The mean annual incidence of lymphatic malignancies was 3.1/10(5) in the Israeli Jews, 2.3/10(5) in the Israeli Arabs and 2.5/10(5) in the Gaza Strip. In the Jewish population there was a peak in the incidence of lymphatic malignancies at the 2-5 years age group, while in the Israeli Arabs this was less prominent. There were no significant differences in the incidence or type of lymphatic malignancies in the various Jewish or Arab groups but there was a trend for a high leukemia to lymphoma ratio (LLR) in the patients from the Gaza Strip. A relatively higher LLR was observed in families of a high socioeconomic status, but it did not reach statistical significance. T-cell ALL comprised about a third of the typed ALL cases. A high proportion of the patients with ALL belonged to the high-risk category: 46% of the Jewish children and 76% of the Gaza Strip children. White blood cell count above 100,000/mm3 were found at presentation in 36.7% of the Gaza Strip patients but only in 9.4% of the Jewish patients. In spite of that, the survival at 4 years of the Jewish and Arab patients was similar. However, the patients with T-cell ALL had a significantly worse survival than the standard risk or the non-T high-risk group: 43.3 +/- 9.7, 66.6 +/- 7.1 and 63.6 +/- 10.4%, respectively. Compared to a previous study conducted in this country in the sixties it appears that the epidemiologic differences that were observed at that time between the various Jewish ethnic groups have practically disappeared.

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma constitute 42% to 45% of the cancers in infants, children, and adolescents: In 1985, an estimated 2025 children were newly diagnosed with these two cancers and 900 (43%) of the pediatric cancer deaths in the United States have been projected to be due to these diseases. The single most important obstacle to preventing these deaths is relapse, and prevention of relapse or salvage of the patient who has had a relapse continues to be a major therapeutic challenge. The most important initial step in the treatment of the child whose disease has relapsed is to determine, to the extent possible, the prognosis. In a child with non-Hodgkin's lymphoma, a relapse confers an extremely poor prognosis, regardless of site of relapse, tumor histology, or other original prognostic factors, prior therapy, or time to relapse. In the child with acute lymphoblastic leukemia in relapse, the prognosis depends on multiple factors. The primary therapy is chemotherapy or chemoradiotherapy with marrow grafting. Other options exist, including no therapy, or investigational therapy. The therapy selected should be predicated on the prognosis. In the child with an isolated central nervous system (CNS) relapse off therapy, minimum therapy should be administered, particularly if the relapse occurred without prior cranial irradiation. In the child whose relapse is more than 6 months off therapy, conventional therapy should be considered. Also, a patient with an isolated CNS relapse on therapy after prior cranial irradiation should be given moderate therapy. Bone marrow transplantation or high-dose chemoradiotherapy with autologous marrow rescue should be reserved in children with a second or subsequent extramedullary relapse, and possibly for those with a first isolated overt testicular relapse on therapy.

Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.