Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease.

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10-20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study.

Serum selenium concentration at diagnosis and outcome in patients with haematological malignancies.

We have previously reported presentation serum selenium level to be predictive of outcome in diffuse large B-cell lymphoma. This has now been studied in a further 430 patients, 163 with acute myeloid leukaemia (AML), 156 with Hodgkin Lymphoma (HL), and 111 with Follicular Lymphoma (FL). Serum selenium was below the UK normal reference range in 45% of patients, and correlated with serum albumin (r=0·24-0·46, P<0·001-0·003) in all tumour types. Independent predictors of presentation selenium were; French-American-British subtype and albumin (P<0·001 for both) in AML, haemoglobin (P=0·002) and B-symptoms (P=0·01) in HL, and albumin (P<0·001) in FL. In AML and HL, response to first line therapy was lower in patients with low serum selenium, but selenium was no longer predictive of response when other variables were entered into a multivariate model. Low selenium was also associated with a worse overall survival in FL [Hazard Ratio (HR) 2·3, 95% confidence interval (CI) 1·4, 4·0] and a trend to a worse overall survival in AML (HR 1·43, 95% CI 0·96, 2·13) by univariate Cox regression analysis, but not by multivariate analysis. In conclusion, low serum selenium is associated with a worse outcome in patients with haematological malignancies, but is not independently predictive, suggesting that it reflects other factors.

Epidemiology and management of lymphoma in low-income countries.

Our current knowledge of the epidemiology and treatment outcome of lymphoma in low-income countries is very limited. In the poorest countries only a small proportion of patients have access to treatment while clinical research is almost non-existent. In order to address these problems and discuss potential solutions a Workshop on 'Epidemiology and Management of Lymphoma in Developing Countries: Challenges and Opportunities for International Collaborations' was held during the 10th International Conference on Malignant lymphoma in Lugano, Switzerland in June 2008 under the sponsorship of UICC, ESMO and ESO. We report here a summary of the discussed issues with some reflections on this workshop.

Efficacy of an intensive post-induction chemotherapy regimen for adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia, given predominantly in the out-patient setting.

Intensification of chemotherapy in adults with acute lymphoblastic leukemia (ALL) has improved outcome. The aim of this analysis was to evaluate outcome of patients treated with an intensive regimen based on that used in the German national trials, but adapted in order to enable treatment to be given mainly on an out-patient basis, once complete remission (CR) had been achieved. Between 2000 and 2007, 53 patients with Philadelphia chromosome-negative ALL (40 with B-ALL and 13, T-ALL) received treatment. CR was achieved in 47/53 (89%), with no significant difference in CR rate between B- and T-ALL. At a median follow-up of 6.3 years, 25 patients are alive, 23 (43%) in 1st CR, and 20 have relapsed. No patient died in CR due to treatment-related toxicity. At 5 years, overall survival was 50%, and disease-free survival, 53%. Thirty four of the 47 patients in whom CR was achieved completed therapy and are evaluable for duration of hospital stay and number of Day Unit attendances. The median time in hospital during the year of treatment was 10 weeks (range, 6-44) with no significant difference between patients ≤ vs. >30 years old. It was possible to administer this intensive protocol largely on an out-patient basis without compromising patient safety.

Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia.

The combination of bortezomib and rituximab was evaluated in patients with mantle cell lymphoma (MCL), follicular lymphoma (FL) and Waldenström macroglobulinaemia (WM), in a Phase I and later, a randomized Phase II study. In the randomized study, 42 patients with recurrent/refractory disease received either: bortezomib 1·3 mg/m(2) on days 1, 4, 8 and 11 of a 3-week cycle with rituximab 375 mg/m(2) on day 1 (21 patients) or: bortezomib 1·6 mg/m(2) and rituximab on days 1, 8, 15 and 22 of a 5-week cycle (with rituximab being given only in cycles 1 and 4).Twenty-eight patients were withdrawn (toxicity 16, progression 7, and 'patient choice' 5). The main toxicities were neurological, gastro-intestinal and haematological. The overall response rate was 28/42(67%) and by histology: MCL 11/19, FL 8/15, and WM 9/10. Ten of 28 responding patients remained progression-free at 1-3·5 years. Toxicity and efficacy were equivalent between the two groups. The combination has significant toxicity but is effective, particularly in patients with WM.

Surveillance investigations after high-dose therapy with stem cell rescue for recurrent follicular lymphoma have no impact on management.

BACKGROUND: The impact of active surveillance, comprising annual computed tomography scanning and bone marrow biopsies, in the follow-up of patients after high-dose therapy with autologous stem cell rescue for recurrent follicular lymphoma was analyzed. DESIGN AND METHODS: Seventy-one of 99 patients who received high-dose therapy commenced the surveillance program. Response duration, time to next treatment and overall survival were compared according to whether disease progression had been diagnosed on the basis of surveillance investigations or on clinical grounds. RESULTS: After a median follow-up of 16 years, progression was documented by surveillance in 16 patients and clinically in 18, the median response duration being 2.4 and 2.3 years, respectively (P=NS). Ten patients with a relapse detected clinically started treatment immediately, contrasting with one patient whose relapse was detected by surveillance investigations. Five patients with relapses detected by surveillance investigations have not required treatment after a median follow-up of 18 years, whereas all but two patients with a relapse detected clinically have been treated. The median time to next treatment was 7 years for patients with a relapse identified by surveillance investigations and 4 years for those whose relapse was manifested clinically (P=0.03). Overall survival was not significantly different between the two groups. CONCLUSIONS: Surveillance investigations, consisting of annual computed tomography scanning and bone marrow biopsies, have no impact on the management of patients with recurrent follicular lymphoma and do not improve the outcome of these patients.

Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis.

Hairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long-term outlook. Median follow-up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse-free survival was 16 years. After relapse (n = 79) or non-response (n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse-free survival was 11 years. After third-line therapy (n = 23), 50% achieved CR and median relapse-free survival was 6.5 years. However, CRs were equally durable, whether after first, second or third-line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 x 10(9)/l before treatment had the longest relapse-free survival (P < 0.0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL-related causes. Patients achieving a CR can expect a normal lifespan.

Rationale for consolidation to improve progression-free survival in patients with non-Hodgkin's lymphoma: a review of the evidence.

Non-Hodgkin's lymphoma (NHL) comprises both indolent forms, including follicular lymphoma (FL) and marginal zone lymphoma (MZL), and aggressive forms, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). FL and DLBCL are the most common subtypes of indolent and aggressive NHL, respectively. Although these lymphomas exhibit different clinical behaviors and outcomes, the prognosis is negatively affected in both DLBCL and FL by the lack of a complete response (CR) with standard treatment options. The aim of therapy should therefore be achievement of a CR, which is not only associated with longer progression-free survival (PFS) and overall survival times, but is also a prerequisite for a cure, particularly in DLBCL. Consolidation treatment with radioimmunotherapy (RIT) is an innovative treatment approach to increase CR rates. Phase II studies have indicated promising results with yttrium-90 ((90)Y)-ibritumomab tiuxetan and iodine-131 ((131)I)-tositumomab as consolidation following induction therapy for previously untreated patients with advanced FL. More recently, investigators reported a marked increase in CR rates and significant improvements in PFS using standard chemotherapy regimens followed by (90)Y-ibritumomab tiuxetan in a phase III randomized trial in patients with previously untreated FL. Data also suggest that RIT may play a role in the treatment of high-risk DLBCL, with encouraging PFS results from a phase II trial of (90)Y-ibritumomab tiuxetan consolidation following induction with rituximab plus chemotherapy in elderly patients with previously untreated DLBCL. With the higher CR rates and longer PFS times observed in patients with FL and DLBCL, as well as encouraging early data from MZL and MCL consolidation trials, RIT appears to have an important role in the treatment of patients with NHL.

Primary follicular lymphoma of the testis and epididymis in adults.

Primary testicular lymphomas typically occur in patients over 60 years of age. Most are diffuse large B-cell lymphomas with frequent dissemination and a poor prognosis. Primary follicular lymphoma of the adult testis has not been well characterized. However, a small number of primary testicular follicular lymphomas have recently been described in children. These showed stage 1E disease, a lack of BCL2 gene rearrangement and Bcl-2 protein expression, and a good clinical outcome. Here, we describe 5 cases of primary follicular lymphoma of the testis and epididymis in adults. These presented as unilateral testicular masses 12 to 40 mm in diameter and were characterized histologically by small neoplastic follicles in a sclerotic background. The neoplastic cells expressed CD10 and Bcl-6, but not Bcl-2 and lacked t(14;18)(q32;q21)/IGH-BCL2 and BCL6 gene rearrangements. Four of the five patients were 35 years old or younger, and 4 presented with stage 1EA disease. Although follow-up is 12 months or less in 2 of the 5 patients, to date each has followed an indolent clinical course. These features are different from those of most adult nodal follicular lymphomas but are very similar to those of the pediatric primary testicular follicular lymphomas. Together, the pediatric and adult cases represent a discrete clinicopathologic entity of t(14;18)(q32;q21)/IGH-BCL2-negative primary follicular lymphoma of the testis and epididymis, which typically present as clinically indolent localized disease in young males and should be distinguished from the diffuse large B-cell lymphoma more frequently seen in the testes of older adults.

Presentation serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin's lymphoma.

PURPOSE: This study was undertaken to test the hypothesis that serum selenium concentration at presentation correlates with dose delivery, first treatment response, and overall survival in patients with aggressive B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: The patients presented between July 1986 and March 1999 and received anthracycline-based chemotherapy, radiotherapy, or both. The total selenium content was retrospectively analyzed in 100 sera, frozen at presentation, using inductively coupled plasma mass spectrometry. RESULTS: The serum selenium concentration ranged from 0.33 to 1.51 micromol/L (mean, 0.92 micromol/L; United Kingdom adult reference range, 1.07 to 1.88 micromol/L). Serum selenium concentration correlated closely with performance status but with no other clinical variable. Multivariate analysis revealed that increased dose delivery, summarized by an area under the curve, correlated positively with younger age (P <.001), advanced stage (P =.001), and higher serum selenium concentration (P =.032). Selenium level also correlated positively with response (odds ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.90; P =.011) and achievement of long-term remission after first treatment (log-rank test, 4.38; P =.036). On multivariate analysis, selenium concentration was positively predictive of overall survival (hazard ratio [HR], 0.76 for 0.2 micromol/L increase; 95% CI, 0.60 to 0.95; P =.018), whereas age indicated negative borderline significance (HR, 1.09; 95% CI, 0.99 to 1.18; P =.066). CONCLUSION: Serum selenium concentration at presentation is a prognostic factor, predicting positively for dose delivery, treatment response, and long-term survival in aggressive non-Hodgkin's lymphoma. Unlike most existing prognostic factors in aggressive non-Hodgkin's lymphoma, selenium supplementation may offer a novel therapeutic strategy in this frequently curable malignancy.

The clinical course of follicular lymphoma.

Follicular lymphoma serves as a paradigm for the other subtypes of non-Hodgkin's lymphoma previously collectively known as 'indolent' or 'low-grade'. As such, its clinical course (that is, the natural history as influenced by conventional therapy) can act as a useful baseline against which the efficacy of new approaches may be assessed. The illness is characterised by repeated responsiveness to treatment but typically this is transient and incomplete. Death occurs at a median of 9-10 years after diagnosis, generally as a consequence of resistant disease, transformation to diffuse large B cell pathology or as a result of side effects of therapy. It has been demonstrated that there is no survival advantage associated with starting treatment prior to there being a clinical need to do so. It is hoped that the advent of new treatment modalities will alter the inexorable pattern of recurrence.

High-dose treatment with autologous haemopoietic progenitor cell support for large B-cell, follicular and mantle-cell lymphoma.

The purpose of this chapter is to review the available information on the use of high-dose treatment (HDT) in large B-cell, follicular and mantle-cell lymphoma. The last 10 years have seen a dramatic increase in the number of patients receiving high-dose treatment with autologous haemopoietic progenitor cell support for non-Hodgkin's lymphoma. In patients with recurrent large B-cell lymphoma, HDT is now accepted as the 'standard of care', provided responsiveness to conventional chemotherapy at the time of recurrence has been demonstrated. In contrast, the situation in newly diagnosed patients is far from clear. Several phase III studies have been conducted, comparing conventional chemotherapy with either: the same treatment followed by HDT or an abbreviated number of cycles of conventional therapy followed by HDT. The results hitherto have not conclusively shown an advantage for HDT. In mantle-cell and follicular lymphoma, HDT should still be regarded as experimental. Current studies are evaluating the use of anti-CD20, given either as part of the treatment prior to HDT or as maintenance therapy. In view of the propensity for both of these illnesses to involve the bone marrow, a number of studies have addressed the question of in vitro treatment of the stem cell product. The advent of PCR analysis has made it possible to evaluate the significance of 'molecular remission'. In follicular lymphoma, there is a correlation between freedom from recurrence and persistent PCR negativity for bcl-2 rearrangement-containing cells in follow-up bone marrow samples.

Acute myelogenous leukaemia in older patients at St Bartholomew's Hospital: outcome with mitoxantrone and cytarabine.

Elderly patients (age >60 years) with AML who are selected for curative treatment frequently receive anthracycline/cytarabine containing regimens. The anthracendione mitoxantrone (MTN) in combination with cytarabine (Ara-C) produces comparable complete remission rates to other regimens and may be less toxic. Over a 12 year period, 75 patients (median age 67 years, range 60-83 years) referred with newly diagnosed AML were treated with MTN and ara-C. MTN was administered at 12 mg/m(2)/day intravenously for three days in the first 26 patients, and 10 mg/m(2)/day intravenously for five days in a subsequent 49 patients. Ara-C was administered at a dose of 100 mg/m(2) twice daily intravenously for seven days. Complete remission (CR) was achieved in 34 out of 75 patients (45%). The median disease-free survival overall was 7.5 months (one month to nine and a half years). The median survival was one year for patients in whom CR was achieved, compared to four months in patients whom treatment failed (P=0.001). Age alone was predictive of achievement of CR, whilst presentation karyotype, serum LDH and patient age correlated with overall survival. These results confirm that although elderly patients have a poor outcome, prognostic factors can be identified that influence treatment outcome in this important group of patients.

Comparative genomic hybridization and multiplex-fluorescence in situ hybridization: an appraisal in elderly patients with acute myelogenous leukemia.

Comparative genomic hybridization (CGH) and multiplex-fluorescence in situ hybridization (M-FISH) were used to evaluate the presentation karyotype in 15 and 18 patients respectively, aged >/=60 years, with acute myeloid leukemia (AML). Conventional G-banded analysis was performed in all patients prior to evaluation. Comparative genomic hybridization confirmed the G-banded karyotype fully in 12 patients and partially in two patients. Normal CGH profiles were observed in patients with a normal karyotype and in one patient with a balanced chromosomal translocation as the sole cytogenetic aberration. Multiplex-fluorescence in situ hybridization provided additional information in two patients with a complex karyotype, but failed to detect a telomeric translocation in one patient. Eight patients with normal G-banded karyotypes appeared normal by M-FISH. These results demonstrate that both CGH and M-FISH analysis correlate well with the G-banded karyotype in AML. Furthermore, although additive cytogenetic data was not provided by either technique in cases with normal karyotype, DNA copy number change and cryptic translocations below the resolution of CGH and M-FISH may still be the initiating event for leukemogenesis for these patients.

90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial.

PURPOSE: Updated results are presented after a median follow-up of 7.3 years from the phase III First-Line Indolent Trial of yttrium-90 ((90)Y) -ibritumomab tiuxetan in advanced-stage follicular lymphoma (FL) in first remission. PATIENTS AND METHODS: Patients with CD20(+) stage III or IV FL with complete response (CR), unconfirmed CR (CRu), or partial response (PR) after first-line induction treatment were randomly assigned to (90)Y-ibritumomab consolidation therapy (rituximab 250 mg/m(2) days -7 and 0, then (90)Y-ibritumomab 14.8 MBq/kg day 0; maximum 1,184 MBq) or no further treatment (control). Primary end point was progression-free survival (PFS) from date of random assignment. RESULTS: For 409 patients available for analysis ((90)Y-ibritumomab, n = 207; control, n = 202), estimated 8-year overall PFS was 41% with (90)Y-ibritumomab versus 22% for control (hazard ratio [HR], 0.47; P < .001). For patients in CR/CRu after induction, 8-year PFS with (90)Y-ibritumomab was 48% versus 32% for control (HR, 0.61; P = .008), and for PR patients, it was 33% versus 10% (HR, 0.38; P < .001). For (90)Y-ibritumomab consolidation, median PFS was 4.1 years (v 1.1 years for control; P < .001). Median time to next treatment (TTNT) was 8.1 years for (90)Y-ibritumomab versus 3.0 years for control (P < .001) with approximately 80% response rates to second-line therapy in either arm, including autologous stem-cell transplantation. No unexpected toxicities emerged during long-term follow-up. Estimated between-group 8-year overall survival rates were similar. Annualized incidence rate of myelodysplastic syndrome/acute myeloblastic leukemia was 0.50% versus 0.07% in (90)Y-ibritumomab and control groups, respectively (P = .042). CONCLUSION: (90)Y-ibritumomab consolidation after achieving PR or CR/CRu to induction confers 3-year benefit in median PFS with durable 19% PFS advantage at 8 years and improves TTNT by 5.1 years for patients with advanced FL.

Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab.

PURPOSE: Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. RESULTS: In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m(2)) was confirmed to be the same as that for single-agent INO (1.8 mg/m(2)). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. CONCLUSION: R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20(+)/CD22(+) B-cell NHL.

Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study.

PURPOSE: We investigated the long-term risk of second primary malignancy after chemotherapy for Hodgkin's lymphoma (HL) in a much larger cohort than any yet published, to our knowledge. PATIENTS AND METHODS: We followed 5,798 patients with HL treated with chemotherapy in Britain from 1963 to 2001--of whom 3,432 also received radiotherapy--to assess second primary malignancy risks compared with general population-based expectations. RESULTS: Second malignancies occurred in 459 cohort members. Relative risk (RR) of second cancer was raised after chemotherapy alone (RR, 2.0; 95% CI, 1.7 to 2.4) but was much lower than after combined modalities (RR, 3.9; 95% CI, 3.5 to 4.4). After chemotherapy alone, there were significantly raised risks of lung cancer, non-HL, and leukemia, each contributing approximately equal absolute excess risk. After combined modalities, there were raised risks of these and several other cancers. Second cancer risk peaked 5 to 9 years after chemotherapy alone, but it remained raised for 25 years and longer after combined modalities. Risk was raised after each common chemotherapy regimen except, based on limited numbers and follow-up, adriamycin, bleomycin, vinblastine, and dacarbazine. The age and time-course relations of lung cancer differed between chemotherapy alone and combined modalities. CONCLUSION: Although chemotherapy alone leads to raised risk of second malignancy, this risk is lower and affects fewer anatomic sites than that after combined modalities, and it is slight if at all after 15 years follow-up. The mechanism of lung cancer etiology may differ between chemotherapy and radiotherapy.

Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study.

PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.